CoChat
Sign Up
Cited by 2,187RNA and protein synthesis mechanismsRNA Research and SplicingGenomics and Phylogenetic Studies

Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity and Dynamics of Mammalian Proteomes

Open access
Ingolia, Nicholas T., Lareau, Liana F., Weissman, Jonathan S.·2011·Cell
DOI 10.1016/j.cell.2011.10.002PMC PMC3225288
Open this paper in CoChat — free accountOpen PDF

Abstract

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.

Integrity signals

Registry

Crossref · 10.1016/j.cell.2011.10.002

Cites

86 of 86 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 35 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    In E14 mouse embryonic stem cells, the amount of protein produced per transcript varies over more than a 10-fold range.

    “there was a broad distribution encompassing over a 10-fold range in the amount of protein produced per transcript”
    Quote in the paperSubstantial claim
  • Findingown data

    Emetine-treated cells yield slightly longer ribosome footprints than untreated or cycloheximide-treated cells.

    “Footprints derived from emetine-treated cells are slightly longer than those from untreated or cycloheximide-treated cells”
    Quote in the paperNot a substantial claim
  • Findingown data

    Elongation inhibitors alter the pattern of ribosome footprints along transcripts.

    “Nonetheless, elongation inhibitors do alter the pattern of ribosome footprints along transcripts.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Drug pre-treatment eliminates the excess of ribosomes seen at the stop codon in untreated cells.

    “Drug pre-treatment also eliminates the excess of ribosomes seen at the stop codon in untreated cells”
    Quote in the paperSubstantial claim
  • Findingown data

    In mammalian translation, pronounced pauses occur where ribosome density is 25-fold or greater than the median density across the gene body.

    “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”
    Quote in the paperSubstantial claim
  • May combine two claims. 32
  • Classified as probably not a substantial claim. 15

  • May combine two claims.

    Findingown data

    Ribosomes at stop codons have longer footprints, suggesting a different conformation.

    “Interestingly, we saw longer footprints at stop codons (Figure 1B and S1B), suggesting that the accumulating ribosomes are in a different conformation”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    Drug-treated cells show an excess of ribosomes at the initiation site and over the first five to ten codons, while untreated cells lack this excess.

    “The excess of ribosomes at the initiation site and extending over the first five to ten codons is essentially absent from untreated cells”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There is no evidence for termination pausing in the majority of other tail-anchored proteins (3 of 32 have pauses), nor is it restricted to tail-anchored proteins.

    “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”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Strong pauses are enriched for glutamate or aspartate in the A site, preceded by proline or glycine and then another proline, with additional bias toward the GAA glutamate codon and CC(A/T) proline codons.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Pausing does not cause secondary ribosome accumulation about 10 codons upstream nor depletion within the 10-codon shadow.

    “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”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Wolin and Walter, 1988

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The Xbp1 pause is confirmed and its precise position is residue Asn 256, the last codon required for translational arrest.

    “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”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Yanagitani et al., 2011 source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    The majority (65%) of these transcripts contain more than one detectable translation initiation site, and 16% contain four or more sites.

    “The majority (65%) of these transcripts contain more than one detectable site of translation initiation, with 16 percent containing four or more sites”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Elongation kinetics are independent of length and protein abundance and are the same in secreted proteins.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    They identified 570 genes with potential N-terminal extensions and 870 with N-terminal truncations among the 4994 genes analyzed.

    “We identified 570 genes with potential N-terminal extensions and 870 with N-terminal truncations in the 4994 genes we analyzed.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Nearly half (44%) of the AUG initiation sites found are unannotated, and the majority of these are downstream of the annotated start and predicted to produce N-terminally truncated proteins or ORFs in alternate reading frames.

    “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”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Igf2 has two 5′ UTR variants with the same reading frame annotated in both transcripts, but they observed an isoform-specific N-terminal extension.

    “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”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    They found an N-terminal extension on the DNA repair protein Swi5; its protein sequence is conserved and experimental evidence indicates endogenous mouse Swi5 is larger than the annotated 89 amino acid protein.

    “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”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Akamatsu and Jasin, 2010

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Myc and Nanog both have multiple uORFs and alternate translation products initiating at both AUG and near-cognate sites.

    “both have multiple uORFs and alternate translation products initiating at both AUG and near-cognate sites”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    The differentiation process involved reduced Klf4, loss of Oct4, and increased expression of developmental and lineage-specific genes.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Niwa et al., 2009 source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    The Pih1d1 gene possesses two 5′ UTR isoforms, each containing a different uORF.

    “The gene Pih1d1 has two 5′ UTR variants with distinct uORFs.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Mammalian protein-coding genes show widespread upstream translation, which is more extensive than the upstream translation previously seen in yeast.

    “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).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Ingolia et al., 2009 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    The data are consistent with prior work that inferred translation levels from absolute mRNA and protein abundance measurements.

    “Our data are consistent with recent work that indirectly infers translation levels from absolute mRNA and protein abundance measurements”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Schwanhausser et al., 2011 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Translation was the single largest contributor to protein abundance in prior work.

    “they found that translation was the single largest contributor to protein abundance”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Schwanhausser et al., 2011 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The distribution of protein produced per transcript is asymmetric, suggesting a maximal rate of protein production and substantial dynamic range for decreased translational efficiency.

    “This distribution is asymmetric, suggesting a maximal rate of protein production from an mRNA and substantial dynamic range for decreased translational efficiency.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    Brief treatment of cells with elongation inhibitors did not significantly change which transcripts were ribosome-associated and did not distort overall translation measurements made by ribosome profiling.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    tRNA identity and nascent peptide sequence can influence elongation kinetics, whereas even for rare codons tRNA recruitment is not rate-limiting.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Harringtonine binds free 60S subunits but not those joined into an 80S ribosome; elongating ribosomes are immune, and a 60S subunit bound by harringtonine forms an 80S at a start site that does not move forward.

    “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”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Fresno et al., 1977 source

      Not checked in the free run.

    • cites Robert et al., 2009 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Actual false negative and false positive rates may be lower because not all annotated start sites are correct and there is substantial non-canonical initiation.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Extensions most often resulted from near-cognate initiation, probably because computational gene annotation selects the first in-frame AUG.

    “Extensions most often resulted from near-cognate initiation (Figure S2B), probably because computational gene annotation selects the first in-frame AUG”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    They classify these RNAs as short, polycistronic, ribosome-associated coding RNAs (sprcRNAs) based on the observation that they contain small coding sequences bound by elongating ribosomes and frequently contain multiple ORFs.

    “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.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The first uORF in the Atf4 transcript is constitutively translated and ribosomes then reinitiate at either the second uORF or the CDS.

    “The first uORF in the Atf4 transcript is constitutively translated and ribosomes then reinitiate at either the second uORF or the CDS”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Calvo et al., 2009 source

      Not checked in the free run.

    • cites Lu et al., 2004

      Not checked in the free run.

    • cites Morris and Geballe, 2000

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    These data establish that the majority of lincRNAs are exported to the cytoplasm and effectively engaged by the protein translation machinery.

    “These data establish that the majority of lincRNAs are exported to the cytoplasm and effectively engaged by the protein translation machinery.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    uORFs have two roles: some permit downstream reinitiation, whereas others capture some fraction of scanning pre-initiation complexes and decrease CDS translation.

    “This exemplifies two roles of uORFs—some permit downstream reinitiation, whereas others capture some fraction of scanning pre-initiation complexes and decrease CDS translation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Internal initiation in the Ets family transcription factor Etv5 produces a product that lacks the predicted activation domain but contains the DNA-binding domain.

    “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)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Monte et al., 1996 source

      Not checked in the free run.

    • cites Monte et al., 1994

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Alternative splicing generates transcripts with different upstream initiation sites and results in different uORF translation.

    “Thus, alternative splicing generates transcripts with different upstream initiation sites and results in different uORF translation.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Prior polysome profiling work indicated a global rise in cellular translation during early embryonic stem cell differentiation.

    “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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Sampath et al., 2008 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    A similar shift in upstream translation has been linked to proliferation in cancer and to the translational control of ribosomal proteins.

    “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).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Mamane et al., 2006 source

      Not checked in the free run.

    • cites Ruggero and Sonenberg, 2005

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    A set of well-expressed genes was chosen based on median footprint density across the coding sequence, omitting the first 15 and last 5 codons because ribosomes accumulate there.

    “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).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Non-AUG initiation has been implicated in generating peptides for immune surveillance.

    “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.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Malarkannan et al., 1999 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Ribosome profiling provides detailed information on the kinetics and mechanism of translation elongation and on coupled co-translational events.

    “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.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Metagene profiles from harringtonine run-off were normalized using the median value over codons 800-1000, a region that appeared undepleted at the treatment times used.

    “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.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Assigning initiation sites preferentially to AUG codons may cause a modest bias against finding near-cognate initiation.

    “The preferential assignment of initiation sites to AUG codons may lead to a modest bias against detecting near-cognate initiation.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Mass spectrometry and ribosome profiling are highly complementary methods.

    “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.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    The SVMlight tool was trained on 3,200 transcripts, using annotated start codons as positive examples and ten other positions as negative examples.

    “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.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Joachims, 1999

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Initiation sites were called as one or more consecutive positions that exceeded an SVM score cutoff and had at least 50 harringtonine footprints in total across samples.

    “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.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    For most analyses, ribosome footprint alignments were mapped to specific A-site nucleotides using alignment position and length, with calibration from footprints at coding sequence boundaries.

    “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).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Ingolia et al., 2009 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Translation of uORFs can regulate expression of the downstream protein-coding gene in response to either global or gene-specific regulatory signals.

    “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).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Sonenberg and Hinnebusch, 2009 source

      Not checked in the free run.

    • cites Medenbach et al., 2011 source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductcitation

    LincRNAs were taken from reconstructed transcripts that fell entirely within lincRNA chromatin signatures and excluded known protein-coding genes.

    “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.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Guttman et al., 2010 source

      Not checked in the free run.

    • cites Guttman et al., 2009 source

      Not checked in the free run.

43 of 43

  • 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.”
2 of 2

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?

  • Ribosome profiling has 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.

    “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

    The Results section, “Changes in Translation During Embryoid Body Formation” (page unavailable), reports that ribosomal proteins were translated 3- to 4-fold less efficiently than the typical transcript during differentiation. It does not establish that translation rates changed by only several-fold across all expressed genes or that all other genes changed similarly; it also reports a significant efficiency increase for integral membrane proteins. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Ribosome profiling has shown that long non-coding RNAs in the cytosol can be engaged by the polyribosome but do not code for protein.

    “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]

  • Studies that have attempted deliberate co-analysis of RNA and protein have consistently observed a limited correlation (between 0.5-0.7) in abundance.

    “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]

  • Measurements of mRNA abundance alone are insufficient to be considered predictive of protein abundance.

    “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]

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. 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
  2. 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

Related

Authors
Ingolia, N. T., Lareau, L. F., & Weissman, J. S.
Affiliations
  • QB3 (US)
  • Stanford University (US)
Corresponding author
Ingolia, Nicholas T.
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2011-11
Volume
147
Issue
4
Pages
789-802
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2011.10.002
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
Licence
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

About these checks

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-05.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-05.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review