The DOI matches its Crossref record; 86 of the 86 references it cites were found in a registry or an index; none of the 35 sources its claims cite is checked for support yet.
Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity and Dynamics of Mammalian Proteomes
Open accessAbstract
The ability to sequence genomes has far outstripped approaches for deciphering the information they encode. Here we present a suite of techniques, based on ribosome profiling (the deep sequencing of ribosome-protected mRNA fragments), to provide genome-wide maps of protein synthesis as well as a pulse-chase strategy for determining rates of translation elongation. We exploit the propensity of harringtonine to cause ribosomes to accumulate at sites of translation initiation together with a machine learning algorithm to define protein products systematically. Analysis of translation in mouse embryonic stem cells reveals thousands of strong pause sites and unannotated translation products. These include amino-terminal extensions and truncations and upstream open reading frames with regulatory potential, initiated at both AUG and non-AUG codons, whose translation changes after differentiation. We also define a class of short, polycistronic ribosome-associated coding RNAs (sprcRNAs) that encode small proteins. Our studies reveal an unanticipated complexity to mammalian proteomes.
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53 Own result · 29 Not checked yet · 26 Own interpretation · 5 Own method · 1 No basis given
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“there was a broad distribution encompassing over a 10-fold range in the amount of protein produced per transcript”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > A Simplified Mammalian Ribosome Profiling Assay
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“Footprints derived from emetine-treated cells are slightly longer than those from untreated or cycloheximide-treated cells”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > A Simplified Mammalian Ribosome Profiling Assay
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“Nonetheless, elongation inhibitors do alter the pattern of ribosome footprints along transcripts.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > A Simplified Mammalian Ribosome Profiling Assay
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“Drug pre-treatment also eliminates the excess of ribosomes seen at the stop codon in untreated cells”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > A Simplified Mammalian Ribosome Profiling Assay
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“in mammalian translation we find more pronounced pauses where ribosome density is 25-fold or greater than the median density observed across the body of the gene”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Presence of Strong Ribosomal Pauses
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“The accumulation is still seen when cells are lysed in the presence of a non-hydrolyzable GTP analogue, suggesting that it does not result from continued elongation in the lysate”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > A Simplified Mammalian Ribosome Profiling Assay
What the sources say
- Not checked yetcites Stern-Ginossar and Weissman, unpublished data
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“Beyond the initial five to ten-codon window we saw no global variation in ribosome density along coding sequences in any sample.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > A Simplified Mammalian Ribosome Profiling Assay
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“Translation speed is also independent of codon usage”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Monitoring Kinetics of Translation
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“and at termination codons (420 pauses, Table S2C)”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Presence of Strong Ribosomal Pauses
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“Importantly, we see no enrichment for residues or codons downstream of the A-site, which are not yet being decoded.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Presence of Strong Ribosomal Pauses
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“The rate of translation is remarkably consistent between different classes of messages”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Monitoring Kinetics of Translation
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“Following a delay of ~60 seconds, which presumably reflects the time required for engagement of harringtonine, ribosomes progress from the 5′ ends of transcripts at a rate of 5.6 amino acids per second”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Monitoring Kinetics of Translation
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“Analysis of the sequence around the pause sites reveals a consensus peptide motif”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Presence of Strong Ribosomal Pauses
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“Analysis of a distinct testing set of transcripts not used for training established that this model recognized 86 percent of annotated start codons as sites of translation initiation in comparison to only ~1 percent of other positions”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Defining Translation Start Sites
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“we observed a dramatic enrichment for AUG (23-fold; Figure 4E)”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Defining Translation Start Sites
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“Our data confirmed termination pausing during the Sec61b and Vamp translation in vivo”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Presence of Strong Ribosomal Pauses
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“Sites that match the full three-residue consensus have dramatically reduced elongation rates overall”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Presence of Strong Ribosomal Pauses
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“We applied the SVM approach to identify 13454 candidate translation start sites within ~5000 transcripts that were well-expressed in our mouse ES cells”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Defining Translation Start Sites
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“We found that harringtonine treatment also leads to a profound accumulation of ribosomes at the sites of translation initiation”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Defining Translation Start Sites
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“We find thousands of novel pauses in the body of genes (1500 pauses in 1100 genes found in a set of 4994 well-expressed genes; Tables S2A and S2B)”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Presence of Strong Ribosomal Pauses
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“We also see no evidence that the pause sites are enriched for rare codons.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Presence of Strong Ribosomal Pauses
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“These uORF initiation sites are accompanied by elongating ribosome footprints in the untreated sample that are depleted during harringtonine treatment, indicating that they are involved in active translation”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Translation of uORFs
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“We also found a strong enrichment for a specific subset of the near-cognate codons (i.e., codons that differ from AUG by a single nucleotide) at initiation sites”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Defining Translation Start Sites
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“The majority of novel near-cognate initiation sites we detected drive the translation of uORFs”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Translation of uORFs
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“internal initiation in the signaling scaffold Ecsit produces a protein nearly identical to a dominant negative form created by designed N-terminal deletion”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Characterization of Alternate Open Reading Frames
What the sources say
- Not checked yetcites Kopp et al., 1999 source
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“We also identify a significant subset of true lincRNAs that are not translated, including the well-documented RNA element NEAT1”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Exploring Translation of sprcRNAs
What the sources say
- Not checked yetcites Clemson et al., 2009 source
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“However, 280 of the genes with N-terminal truncations lacked detectable initiation on the annotated AUG”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Characterization of Alternate Open Reading Frames
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“We saw specific start sites marked by harringtonine followed by ribosome footprints extending to the first in-frame stop codon”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Exploring Translation of sprcRNAs
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“A substantial fraction (14%) of the initiation sites we observed are predicted to produce alternate protein isoforms of known genes”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Characterization of Alternate Open Reading Frames
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“Remarkably, the majority of putative lincRNAs contain regions of high translation comparable to protein-coding genes”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Exploring Translation of sprcRNAs
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“we additionally observed that at least 30% of these genes showed a significant difference in the ratio of ribosome footprint to mRNA-seq reads between the distinct 5′ UTRs of different isoforms”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Translation of uORFs
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“Strong initiation of the uORF in one isoform led to 50% less initiation of its protein-coding reading frame as compared to initiation of the same protein-coding reading frame in the second isoform (Figure S3).”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Translation of uORFs
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“Translation of uORFs also declined substantially during differentiation.”
- Also stated in: § DISCUSSION · boosted
“We have shown that upstream translation decreases as ES cells undergo differentiation, indicating that it is subject to regulation and may be part of a major program of translational control.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Changes in Translation During Embryoid Body Formation
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“The gene Pih1d1 has two 5′ UTR variants with distinct uORFs.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Translation of uORFs
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“This shift can be observed on the 5′UTR of individual genes with defined uORFs (Figures 7C and 7D).”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Changes in Translation During Embryoid Body Formation
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“Although these genes were still highly expressed in embryoid bodies, they were translated 3- to 4-fold less efficiently than the typical transcript (Tables S5D-S5F).”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Changes in Translation During Embryoid Body Formation
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“We measured the level of upstream translation using the ratio of ribosome footprint reads in the 5′UTR to the coding sequence of each gene and found that the typical transcript showed a ~25% decrease in 5′UTR translation during differentiation (Figure 7B).”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Changes in Translation During Embryoid Body Formation
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“We also observed a modest but quite significant increase in the translational efficiency of integral membrane proteins in EBs (Figure S4E and Table S5F), which could result directly from a redirection of ribosomes to the rough ER, or indirectly through regulatory programs whose targets are enriched for membrane proteins.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Changes in Translation During Embryoid Body Formation
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“we found 1800 genes showing differential initiation of uORFs in distinct 5′ UTR isoforms”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Translation of uORFs
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“Polysome profiling experiments have suggested a global increase in cellular translation during early ES cell differentiation, and we see a modest upregulation of RPs in our early timepoint (Sampath et al., 2008).”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Changes in Translation During Embryoid Body Formation
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“Alternative inclusion of uORFs was also seen in ribosomal proteins, including Rps27a, where a small fraction of transcripts had a retained 5′ UTR intron that introduced a uORF”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Translation of uORFs
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“Withdrawal of leukemia inhibitory factor (LIF) induced differentiation (Figure S4A), which we assessed visually and by the down-regulation of the direct LIF target Klf4 (Niwa et al., 2009), followed by loss of Oct4 expression and the induction of developmental and lineage-specific genes (Figures S4B and S4C and Tables S5A-S5F).”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Changes in Translation During Embryoid Body Formation
What the sources say
- Not checked yetcites Niwa et al., 2009 source
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“We then looked for translational control of gene expression during differentiation and observed strong repression of ribosomal proteins (RPs) in EBs relative to ES cells (Figure 7A, Figure S5D and Table S5F).”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Changes in Translation During Embryoid Body Formation
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In the paper
“We observe robust translation initiation at a distinct uORF in this second isoform”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Translation of uORFs
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In the paper
“A number of novel features of mammalian proteomes emerge from our studies, including the ubiquitous use of alternate initiation sites that drive the production of extended or truncated isoforms of known proteins as well as the translation of sprcRNAs, whose protein-coding potential was not initially apparent.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > DISCUSSION
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In the paper
“A number of novel features of mammalian proteomes emerge from our studies, including the ubiquitous use of alternate initiation sites that drive the production of extended or truncated isoforms of known proteins as well as the translation of sprcRNAs, whose protein-coding potential was not initially apparent.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > DISCUSSION
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In the paper
“It is also regulated during EB formation, suggesting a global link with growth and proliferation, and is involved in the synthesis of functional proteins, including the well-studied oncogene and pluripotency factor Myc (Hann et al., 1988).”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > DISCUSSION
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In the paper
“While most productive protein synthesis starts at a classical AUG codon, initiation at CUG and GUG codons is widespread and is likely to have broad biological significance.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > DISCUSSION
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In the paper
“Our studies also establish that many sites of translation initiation, especially upstream initiation, occur at non-AUG codons.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > DISCUSSION
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In the paper
“While it is possible that such a ramping effect occurs in S. cerevisiae, it does not appear to occur mammalian cells.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > A Simplified Mammalian Ribosome Profiling Assay
What the sources say
- Not checked yetcites Tuller et al., 2010 source
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In the paper
“Based on a typical elongation rate of ~6 codons per second (see below) the pauses we see last for several seconds”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Presence of Strong Ribosomal Pauses
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In the paper
“which is enough time for the paused ribosome-nascent chain (RNC) complex to bind co-translational chaperones”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Presence of Strong Ribosomal Pauses
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In the paper
“An important practical implication for the universality of the average rate of elongation is that ribosome footprint density provides a reliable measure of protein synthesis independent of the particular gene being translated.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Monitoring Kinetics of Translation
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In the paper
“Instead, pausing at termination codons is a common feature of translation.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Presence of Strong Ribosomal Pauses
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In the paper
“The lack of packed ribosomes at pause sites suggests that ribosome density is typically too low to cause frequent encounters between upstream elongating ribosomes and a transiently stalled downstream ribosome”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Presence of Strong Ribosomal Pauses
What the sources say
- Not checked yetcites Arava et al., 2003 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The absence of downstream depletion also argues that the majority of ribosomes continue elongation following these pause sites.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Presence of Strong Ribosomal Pauses
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In the paper
“Initiation at near-cognate sites is sometimes resistant to harringtonine (Starck et al., 2008); Stern-Ginossar and Weissman, unpublished data), so our analysis may underestimate the true prevalence of near-cognate initiation.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Defining Translation Start Sites
What the sources say
- Not checked yetcites Starck et al., 2008 source
- Not checked yetcites Stern-Ginossar and Weissman, unpublished data
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Our observations suggest that near-cognate uORFs are quite common.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Translation of uORFs
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In the paper
“Our approaches provide experimentally based maps of the protein coding potential of complex genomes, and reveal in depth information about the kinetics and mechanism of translation elongation and coupled co-translational events.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > DISCUSSION
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In the paper
“It reflects a broad change in the translational apparatus with the potential to impact gene expression genome-wide.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Changes in Translation During Embryoid Body Formation
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In the paper
“This effect demonstrates the potential impact of the widespread upstream initiation we observe in both alternative and constitutive 5′ UTRs.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Translation of uORFs
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In the paper
“Here we present a range of ribosome profiling techniques, based on deep sequencing of ribosome-protected fragments, that dramatically expand our ability to define and quantitatively monitor mammalian proteomes.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > DISCUSSION
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In the paper
“The translation of RPs is regulated in response to proliferation and nutrient status (Hamilton et al., 2006), and here we show that this response is a notable feature of EB formation.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Changes in Translation During Embryoid Body Formation
What the sources say
- Not checked yetcites Hamilton et al., 2006 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The bias towards upstream non-AUG initiation seems to conflict with a pure scanning model for start codon recognition, as a pre-initiation complex that bypasses the annotated AUG is no less likely to recognize a subsequent CUG, though the difference could reflect heterogeneous stringencies in scanning complexes.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > DISCUSSION
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In the paper
“Non-AUG initiation clearly impacts many aspects of translation.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > DISCUSSION
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In the paper
“We have shown that upstream translation decreases as ES cells undergo differentiation, indicating that it is subject to regulation and may be part of a major program of translational control.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > DISCUSSION
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In the paper
“While most productive protein synthesis starts at a classical AUG codon, initiation at CUG and GUG codons is widespread and is likely to have broad biological significance.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > DISCUSSION
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In the paper
“Finally, ribosome profiling allows high precision, genome-wide measures of the rate of protein synthesis from the density of ribosome footprints, much as RNA-seq experiments measure mRNA abundance from read density; such gene expression measurements may represent the most frequent application of ribosome profiling even after the proteome is fully defined.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > DISCUSSION
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In the paper
“The extensive upstream non-AUG initiation we observe is likely to regulate protein synthesis from specific transcripts in response to global changes in initiation.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“It is also regulated during EB formation, suggesting a global link with growth and proliferation, and is involved in the synthesis of functional proteins, including the well-studied oncogene and pluripotency factor Myc (Hann et al., 1988).”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > DISCUSSION
What the sources say
- Not checked yetcites Hann et al., 1988 source
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In the paper
“While there have been remarkable advances in quantitative mass spectrometry (Nilsson et al., 2010), it is difficult to match the large dynamic range and comprehensive nature of deep sequencing.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > DISCUSSION
What the sources say
- Not checked yetcites Nilsson et al., 2010 source
plain- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 32
- Probably not a substantial claim. 15
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interestingly, we saw longer footprints at stop codons (Figure 1B and S1B), suggesting that the accumulating ribosomes are in a different conformation”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > A Simplified Mammalian Ribosome Profiling Assay
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In the paper
“The excess of ribosomes at the initiation site and extending over the first five to ten codons is essentially absent from untreated cells”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > A Simplified Mammalian Ribosome Profiling Assay
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“we found no evidence for this phenomenon in the majority of other TA proteins (3 / 32 have pauses), nor was it restricted to TA proteins”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Presence of Strong Ribosomal Pauses
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“There is strong enrichment of glutamate or asparate in the A site at strong pauses, preceded by a proline or glycine and then another proline, with an additional bias towards the GAA glutamate codon and CC(A/T) proline codons.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Presence of Strong Ribosomal Pauses
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“we see no evidence that pausing causes secondary ribosome accumulation ~10 codons upstream, where a following ribosome would collide with the stalled one (Wolin and Walter, 1988), nor a depletion of ribosomes within the 10 codon “shadow” resulting from paused ribosomes”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Presence of Strong Ribosomal Pauses
What the sources say
- Not checked yetcites Wolin and Walter, 1988
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In the paper
“We confirmed the presence of this pause and identified its precise position as residue Asn 256, which is the last codon required for translational arrest”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Presence of Strong Ribosomal Pauses
What the sources say
- Not checked yetcites Yanagitani et al., 2011 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The majority (65%) of these transcripts contain more than one detectable site of translation initiation, with 16 percent containing four or more sites”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Defining Translation Start Sites
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In the paper
“The kinetics of elongation are independent of length and protein abundance and are the same in secreted proteins, whose translation occurs on the ER surface.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Monitoring Kinetics of Translation
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“We identified 570 genes with potential N-terminal extensions and 870 with N-terminal truncations in the 4994 genes we analyzed.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Characterization of Alternate Open Reading Frames
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In the paper
“Nearly half (44%) of the AUG initiation sites that we found are unannotated, and the majority of these were downstream of the annotated start and were predicted to produce N-terminally truncated proteins or ORFs encoded in alternate reading frames”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Characterization of Alternate Open Reading Frames
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In the paper
“the growth factor Igf2 has two 5′ UTR variants with the same reading frame annotated in both transcripts, but we observed an isoform-specific N-terminal extension”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Characterization of Alternate Open Reading Frames
plainSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“We found an N-terminal extension on the DNA repair protein Swi5 (Figure 4G); its protein sequence is conserved, and there is experimental evidence that endogenous mouse Swi5 is larger than the annotated 89 amino acid protein”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Characterization of Alternate Open Reading Frames
What the sources say
- Not checked yetcites Akamatsu and Jasin, 2010
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“both have multiple uORFs and alternate translation products initiating at both AUG and near-cognate sites”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Translation of uORFs
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In the paper
“Withdrawal of leukemia inhibitory factor (LIF) induced differentiation (Figure S4A), which we assessed visually and by the down-regulation of the direct LIF target Klf4 (Niwa et al., 2009), followed by loss of Oct4 expression and the induction of developmental and lineage-specific genes (Figures S4B and S4C and Tables S5A-S5F).”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Changes in Translation During Embryoid Body Formation
What the sources say
- Not checked yetcites Niwa et al., 2009 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The gene Pih1d1 has two 5′ UTR variants with distinct uORFs.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Translation of uORFs
plainSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“We also observe widespread translation upstream of mammalian protein-coding genes, similar to but more extensive than upstream translation that we observed in yeast (Ingolia et al., 2009).”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > DISCUSSION
What the sources say
- Not checked yetcites Ingolia et al., 2009 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Our data are consistent with recent work that indirectly infers translation levels from absolute mRNA and protein abundance measurements”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > A Simplified Mammalian Ribosome Profiling Assay
What the sources say
- Not checked yetcites Schwanhausser et al., 2011 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“they found that translation was the single largest contributor to protein abundance”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > A Simplified Mammalian Ribosome Profiling Assay
What the sources say
- Not checked yetcites Schwanhausser et al., 2011 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This distribution is asymmetric, suggesting a maximal rate of protein production from an mRNA and substantial dynamic range for decreased translational efficiency.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > A Simplified Mammalian Ribosome Profiling Assay
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We concluded that brief treatment of cells with elongation inhibitors did not significantly change which transcripts were associated with ribosomes and did not distort translation measurements made by ribosome profiling.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > A Simplified Mammalian Ribosome Profiling Assay
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our findings suggest that tRNA identity and nascent peptide sequence can influence the kinetics of elongation, whereas even for rare codons, tRNA recruitment is not rate-limiting.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Presence of Strong Ribosomal Pauses
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This effect likely occurs because harringtonine binds to free 60s subunits, but not those that are joined into an 80s ribosome. Thus, elongating ribosomes are immune to harringtonine, whereas a 60s subunit bound by harringtonine will form an 80s at a start site that does not move forward”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Defining Translation Start Sites
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Actual false negative and false positive rates may be considerably lower, as not all annotated start sites are correct and there is a substantial rate of translation initiation from non-canonical start sites.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Defining Translation Start Sites
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Extensions most often resulted from near-cognate initiation (Figure S2B), probably because computational gene annotation selects the first in-frame AUG”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Characterization of Alternate Open Reading Frames
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We classify these RNAs as short, polycistronic, ribosome-associated coding RNAs (sprcRNAs) based on our observation that they contain small coding sequences that are bound by elongating ribosomes, and frequently contain multiple ORFs.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Exploring Translation of sprcRNAs
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The first uORF in the Atf4 transcript is constitutively translated and ribosomes then reinitiate at either the second uORF or the CDS”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Translation of uORFs
What the sources say
- Not checked yetcites Calvo et al., 2009 source
- Not checked yetcites Lu et al., 2004
- Not checked yetcites Morris and Geballe, 2000
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data establish that the majority of lincRNAs are exported to the cytoplasm and effectively engaged by the protein translation machinery.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Exploring Translation of sprcRNAs
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This exemplifies two roles of uORFs—some permit downstream reinitiation, whereas others capture some fraction of scanning pre-initiation complexes and decrease CDS translation.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Translation of uORFs
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Internal initiation in the Ets family transcription factor Etv5 produces a product that lacks the predicted activation domain (Monte et al., 1996) but contains the domain that mediates DNA binding (Monte et al., 1994)”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Characterization of Alternate Open Reading Frames
What the sources say
- Not checked yetcites Monte et al., 1996 source
- Not checked yetcites Monte et al., 1994
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, alternative splicing generates transcripts with different upstream initiation sites and results in different uORF translation.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Widespread Translation of uORFs
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Polysome profiling experiments have suggested a global increase in cellular translation during early ES cell differentiation, and we see a modest upregulation of RPs in our early timepoint (Sampath et al., 2008).”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Changes in Translation During Embryoid Body Formation
What the sources say
- Not checked yetcites Sampath et al., 2008 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Such a shift has been associated with proliferation in tumorigenesis, and has been linked to the translational control of RPs (Mamane et al., 2006; Ruggero and Sonenberg, 2005).”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > RESULTS > Changes in Translation During Embryoid Body Formation
What the sources say
- Not checked yetcites Mamane et al., 2006 source
- Not checked yetcites Ruggero and Sonenberg, 2005
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A set of well-expressed genes was selected based on median footprint density across the coding sequence, excluding the first 15 and last 5 codons due to the accumulation of ribosomes (Figures 1C and 1D).”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > EXPERIMENTAL PROCEDURES > Footprint Profile Analysis
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“More broadly, it has been implicated in the production of peptides for immune surveillance (Malarkannan et al., 1999), and additional roles will likely emerge as we understand more about which non-AUG codons are used and how this selection is regulated.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > DISCUSSION
What the sources say
- Not checked yetcites Malarkannan et al., 1999 source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our approaches provide experimentally based maps of the protein coding potential of complex genomes, and reveal in depth information about the kinetics and mechanism of translation elongation and coupled co-translational events.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > DISCUSSION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Metagene profiles from harringtonine run-off were further normalized by the median value over codons 800-1000, which appeared undepleted at harringtonine treatment times used in this study, and smoothed by averaging disjoint 5-codon windows.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > EXPERIMENTAL PROCEDURES > Harringtonine Depletion Profile Analysis
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The preferential assignment of initiation sites to AUG codons may lead to a modest bias against detecting near-cognate initiation.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > EXPERIMENTAL PROCEDURES > Initiation Site Prediction
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“More generally mass spectrometry and ribosome profiling represent highly complementary approaches; for example, comparison between changes in rate of synthesis measured by ribosome profiling and abundance measured by mass spectrometry should reveal examples of regulated degradation of proteins.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > DISCUSSION
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The SVMlight pattern recognition tool (Joachims, 1999) was trained on an arbitrary set of 3200 transcripts, using the annotated start codon as a positive example and ten other positions as negative examples.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > EXPERIMENTAL PROCEDURES > Initiation Site Prediction
What the sources say
- Not checked yetcites Joachims, 1999
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Initiation sites were defined as one or more consecutive nucleotide positions that passed an SVM score threshold as well as a minimum of 50 harringtonine footprints total amongst all samples.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > EXPERIMENTAL PROCEDURES > Initiation Site Prediction
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“For most analyses, footprint alignments were assigned to specific A site nucleotides by using the position and total length of each alignment, calibrated from footprints at the beginning and the end of CDSes (Figures S1A and S1B) as previously described (Ingolia et al., 2009).”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > EXPERIMENTAL PROCEDURES > Footprint Sequence Alignment
What the sources say
- Not checked yetcites Ingolia et al., 2009 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Translation of a uORFs can modulate the expression of the downstream protein-coding gene in response to global (Sonenberg and Hinnebusch, 2009) or gene-specific regulatory signals (Medenbach et al., 2011).”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > DISCUSSION
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“LincRNAs were collected from reconstructed transcripts (Guttman et al., 2010) that lay entirely within the lincRNA chromatin signatures identified by Guttman et al. (Guttman et al., 2009), which excluded known protein-coding genes.”
§ Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity of Mammalian Proteomes > EXPERIMENTAL PROCEDURES > LincRNA Analysis
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
The paper relies on this without support.
The number of ribosome footprints at a codon is proportional to the average time a ribosome dwells there.
“The footprint count on a codon should be proportional to the average ribosome dwell time there”
The paper relies on this without support.
Most productive protein synthesis begins at a classical AUG codon.
“While most productive protein synthesis starts at a classical AUG codon, initiation at CUG and GUG codons is widespread and is likely to have broad biological significance.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Ribosome profiling has also shown that translation rates change only several fold upon cellular differentiation and, with the exception of the translation machinery, the change affects all expressed genes to a similar degree (Ingolia et al., 2011)”
From System wide analyses have underestimated protein abundances and the importance of transcription in mammals (2014) · cites this paper as Ingolia et al., 2011
Experimental — accuracy not yet measuredIn the citing paper
“Ribosome profiling has also shown that long non-coding RNAs in the cytosol, many of which are known to be spliced, capped, and polyadenylated in a similar manner to mRNAs62, can be engaged by the polyribosome56, but do not code for protein63.”
From Decoding neuroproteomics: integrating the genome, translatome and functional anatomy (2014) · cites this paper as [56]
In the citing paper
“Importantly, those studies that have attempted deliberate co-analysis of RNA and protein have consistently observed a limited correlation (between 0.5–0.7) in abundance.”
From Decoding neuroproteomics: integrating the genome, translatome and functional anatomy (2014) · cites this paper as [56]
In the citing paper
“As such, measurements of mRNA abundance alone are insufficient to be considered predictive of protein abundance54–56, reinforcing the requirement for cellular analysis at the proteome level.”
From Decoding neuroproteomics: integrating the genome, translatome and functional anatomy (2014) · cites this paper as [56]
Citations
Cites
Initial sequencing and analysis of the human genome
International Human Genome Sequencing Consortium, Whitehead Institute for Biomedical Research, C. F. G. R., Lander, E. S., Linton, L. M., Birren, B., Nusbaum, C., Zody, M. C., Baldwin, J., Devon, K., Dewar, K., et al. (2001) · Nature · doi:10.1038/35057062 · Cited by 24,216
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849
The sequence of the human genome
Venter, J. C., Adams, M. D., Myers, E. W., Li, P. W., Mural, R. J., Sutton, G. G., Smith, H. O., Yandell, M., Evans, C. A., Holt, R. A., et al. (2001) · Science · doi:10.1126/science.1058040 · Cited by 13,909
Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566 · cited 1×
“with recent work that indirectly infers translation levels from absolute mRNA and protein abundance measurements (Schwanhäusser et al., 2011).”
BackgroundAdvances in kernel methods: support vector learning
Schölkopf, B., Burges, C. J. C., & Smola, A. J. (1999) · doi:10.5555/299094 · Cited by 5,809
Control of inositol 1,4,5-trisphosphate-induced Ca2+ release by cytosolic Ca2+
Bootman, M. D., Missiaen, L., Parys, J. B., SMEDT, H. D., & Casteels, R. (1995) · Biochemical Journal · doi:10.1042/bj3060445 · Cited by 5,131
Making Large-Scale SVM Learning PracticalPreprint
Joachims, T. (1998) · RePEc: Research Papers in Economics · doi:10.17877/de290r-14262 · Cited by 4,517
What is a support vector machine?
Noble, W. S. (2006) · Nature Biotechnology · doi:10.1038/nbt1206-1565 · Cited by 4,450
Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals
Guttman, M., Amit, I., Garber, M., French, C., Lin, M. F., Feldser, D., Huarte, M., Zuk, O., Carey, B. W., Cassady, J. P., et al. (2009) · Nature · doi:10.1038/nature07672 · Cited by 4,098
Niwa, H., Miyazaki, J., & Smith, A. G. (2000) · Nature Genetics · doi:10.1038/74199 · Cited by 3,904
Research works printed but not linked: 2
- Niwa, H., Ogawa, K., Shimosato, D., and Adachi, K. (2009). A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells. Nature 460, 118–122. · DOI · Paper page
- Tremml, G., Singer, M., and Malavarca, R. (2008). Culture of mouse embryonic stem cells. In Current Protocols in Stem Cell Biology Chapter 1, Unit 1C 4. · DOI
Cited by
Sorted by citations
GENCODE: The reference human genome annotation for The ENCODE Project
Harrow, J., Frankish, A., Gonzalez, J. M., Tapanari, E., Diekhans, M., Kokocinski, F., Aken, B. L., Barrell, D., Zadissa, A., Searle, S., et al. (2012) · Genome Research · doi:10.1101/gr.135350.111 · Cited by 4,585
Insights into the regulation of protein abundance from proteomic and transcriptomic analyses
Vogel, C., & Marcotte, E. M. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3185 · Cited by 4,195
Genome Regulation by Long Noncoding RNAs
Rinn, J. L., & Chang, H. Y. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-051410-092902 · Cited by 4,091
Unique features of long non-coding RNA biogenesis and function
Quinn, J. J., & Chang, H. Y. (2015) · Nature Reviews Genetics · doi:10.1038/nrg.2015.10 · Cited by 3,700
lincRNAs: Genomics, Evolution, and Mechanisms
Ulitsky, I., & Bartel, D. P. (2013) · Cell · doi:10.1016/j.cell.2013.06.020 · Cited by 2,652
Metadata
- Authors
- Ingolia, N. T., Lareau, L. F., & Weissman, J. S.
- Affiliations
- QB3 (US)
- Stanford University (US)
- Corresponding author
- Ingolia, Nicholas T.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 147
- Issue
- 4
- Pages
- 789-802
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3225288
- OpenAlex
- W2071849521
- Cited by
- 2,187
- References
- 86
- Citations by year
- 2026: 96 · 2025: 127 · 2024: 136 · 2023: 143 · 2022: 135 · 2021: 153 · 2020: 189 · 2019: 134 · 2018: 167 · 2017: 164 · 2016: 168 · 2015: 154 · 2014: 171 · 2013: 139 · 2012: 102
- FWCI
- 54.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 624 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- Damon Runyon Cancer Research Foundation (DRG-2033-09)
- National Institutes of Health (AG10770)
- National Institute on Aging (P01 AG10770, P01AG010770)
- National Institute of General Medical Sciences (F32GM080853, GM080853)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- ribosome profiling, mouse embryonic stem cells, translation elongation, pause sites, harringtonine, translation initiation, upstream open reading frames, amino-terminal extension, protein truncation, small proteins, proteome complexity, cell differentiation
- MeSH terms
- Algorithms, Animals, Artificial Intelligence, Harringtonines, Kinetics, Peptide Chain Initiation, Translational, Ribosomes, RNA, Protein Biosynthesis, Open Reading Frames, Sequence Analysis, RNA, Genomics, Mice, Embryonic Stem Cells, Embryoid Bodies, High-Throughput Nucleotide Sequencing
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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