Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction

In the paper

“These studies also found that Hu binding sites were mostly located in 3′ UTRs of mRNAs, with a significant portion in introns and relatively few in 5′ UTRs.”

What the sources say

• Supported

  The section ‘PAR-CLIP reproducibly identifies thousands of transcripts directly bound by HuR’ (page unavailable) says most binding sites were in 3′ UTRs and approximately 30–35% were in introns. It counts 5′ UTRs among the remaining categories but does not give their separate percentage; the claim’s ‘relatively few’ is consistent with that distribution. (LLM, conf=0.88)

  cites Lebedeva et al. 2011 source
• Disputed

  The Results section (HuR-RNA interactions and RNA Recognition Element, Figure 2A; page not available) reports 83,141 intronic binding-site clusters versus 22,353 in 3′ UTRs. Thus, although substantial 3′ UTR binding is reported, the claim that most sites are in 3′ UTRs is contrary to this paper's counts. (LLM, conf=0.90)

  Checked by a reasoning model — may be wrong.

  cites Mukherjee et al. 2011 sourceExperimental — accuracy not yet measured
• Partly supported

  The Results and Discussion text and Figure 1 caption report a large proportion of HuR iCLIP sites in 3′ UTRs and many in introns. Our copy does not establish that most sites are in 3′ UTRs or explicitly compare the number in 5′ UTRs, so those parts of the claim are not fully supported. (LLM, conf=0.84)

  cites Uren et al. 2011 sourceExperimental — accuracy not yet measured

In the paper

“In the developing mouse and rat cerebral cortex, HuD mRNA is present in proliferating neuronal stem/progenitor cells in the ventricular zone, neuroblasts migrating in the intermediate zones, and terminally differentiating neurons in the cortical plate (Okano and Darnell 1997; Clayton et al. 1998).”

What the sources say

• Disputed

  The Figure 7 caption and “Hierarchies of mHu mRNA expression in developing neurons” section report mHuD mRNA in the intermediate zone and at diminishing levels in the cortical plate, but say it is very weak or absent in differentiated neurons. The section says mHuD mRNA is first evident in intermediate-zone neurons, contrary to the claim of its presence in proliferating ventricular-zone cells. These observations concern mouse cortex; the passages do not report rat cortex. (LLM, conf=0.88)

  Checked by a reasoning model — may be wrong.

  cites Okano and Darnell 1997 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Clayton et al. 1998 source

In the paper

“Moreover, these interactions require the presence of RNA, since HuR and AUF1 were shown to simultaneously or competitively bind onto exclusive or common, respectively, cis-acting elements in the 3′ UTRs of p21cip1/waf1, Cyclin D, TNFα, and β2-adrenergic receptor mRNAs (Lal et al. 2004; David et al. 2007).”

What the sources say

• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites Lal et al. 2004 sourceExperimental — accuracy not yet measured
• Disputed

  Split into 2 atoms — 0 confirmed, 0 partially supported, 2 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Checked by a reasoning model — may be wrong.

  cites David et al. 2007 sourceExperimental — accuracy not yet measured

In the paper

“In the adult mouse and rodent nervous system, expression of HuD mRNA is mostly restricted to specific neuronal populations, including large pyramidal-like neurons in layer V of the neocortex and cerebellar cortex (Purkinje cells), the four Cornu Amonis (CA1-4) regions of the hippocampus, dorsal root ganglia, and motor neurons in the spinal cord, mitral cells in the olfactory bulb, ganglion and int”

What the sources say

• Partly supported

  The ‘mHu mRNA expression in adult brain’ section (page unavailable) reports HuD mRNA in layer 5 neocortical neurons, hippocampal pyramidal neurons, dorsal root ganglia, and olfactory mitral cells. But the paper explicitly says HuD is absent from Purkinje cells; it also does not identify spinal motor neurons as HuD-expressing, saying instead that spinal-cord neurons predominantly express HuC. (LLM, conf=0.90)

  cites Okano and Darnell 1997 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Clayton et al. 1998 source
• Partly supported

  The Methods and Results (page unavailable) describe HuD as neuron-specific and report its expression in the mouse enteric nervous system. They do not describe the claimed restriction of HuD mRNA to the listed brain regions, dorsal root ganglia, or spinal motor neurons. (LLM, conf=0.84)

  cites D’Autreaux et al. 2011 sourceExperimental — accuracy not yet measured

In the paper

“Instead, the investigators identified three novel consensus motifs that are present in ∼80% of HuD-targeted mRNAs expressed in the mouse forebrain.”

What the sources say

• Supported

  The Results section, “Discovery of new HuD-binding motifs” (page not available), reports that approximately 80% (456 of 572) of HuD-target mRNAs contain at least one of three identified motifs. The paper identifies these targets from mouse brain extracts; the 80% figure does not mean that each mRNA contains all three motifs. (LLM, conf=0.93)

  cites Bolognani et al. 2010 source

In the paper

“In addition to being expressed in various neuronal subpopulations in the CNS and PNS, quantitative RT-PCR and Western blot analysis revealed relatively minor, although significant, HuD mRNA and protein levels in several nonneuronal tissues including lung, testes, liver, pituitary gland, pancreatic β cells, and fiber cells of the lens (Abdelmohsen et al. 2010; Bitel et al. 2010; Lee et al. 2012).”

What the sources say

• ?Not checked — no full text of the sourcecites Abdelmohsen et al. 2010 source
• ?Not checked — no full text of the sourcecites Bitel et al. 2010
• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites Lee et al. 2012 sourceExperimental — accuracy not yet measured

In the paper

“Binding to the poly(A) tail seems to depend on the tail length, since results from in vitro binding assays demonstrated that the longer the poly(A) tail, the higher the affinity of Hu protein binding to its target mRNA (Beckel-Mitchener et al. 2002).”

What the sources say

• Partly supported

  The section “HuD Binds with Higher Affinity to GAP-43 Molecules with Long Poly(A) Tails” reports an eightfold higher affinity for GAP-43 mRNA with an A150 tail than with an A30 tail in an in vitro binding assay. The Discussion clarifies that the assay measured HuD binding to a site in the 3′-UTR as a function of tail length, not direct binding to the poly(A) tail; direct tail binding is presented as consistent with the data, not demonstrated by that assay. Page numbers were not supplied in the passages. (LLM, conf=0.88)

  cites Beckel-Mitchener et al. 2002 sourceExperimental — accuracy not yet measured

In the paper

“Converging findings suggest that HuD is one of the earliest markers of the neuronal phenotype (Good 1995; Okano and Darnell 1997; Wakamatsu and Weston 1997; Hambardzumyan et al. 2009).”

• Also stated in: § CONCLUSION AND PERSPECTIVE · plain

  “The Hu member HuD is one of the earliest markers of the neuronal phenotype and is broadly expressed in the mature nervous system.”

What the sources say

• ?Not checked — no full text of the sourcecites Good 1995 source
• Partly supported

  The Abstract reports mHuD expression in migrating neurons during early cortical development, supporting its association with an early neuronal stage. But the sections “Hierarchies of mHu mRNA expression in developing neurons” and “The role of Hu proteins in neural development” identify mHuB, not mHuD, as expressed in the earliest postmitotic neurons. The paper therefore does not establish HuD as one of the earliest markers of the neuronal phenotype. (LLM, conf=0.84)

  cites Okano and Darnell 1997 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Wakamatsu and Weston 1997 source

In the paper

“In situ hybridization analyses of nELAV expression in the mouse brain at day 14 of embryogenesis (E14) have revealed that the spatial expression of HuD mRNA is also partially unique compared to HuB and HuC (Okano and Darnell 1997), thus further supporting the notion that HuD is not completely functionally redundant.”

What the sources say

• Supported

  The Figure 7 caption describes in situ hybridization of E14 mouse cortex with separate HuB, HuC, and HuD probes. It reports distinct spatial patterns: HuD is intense in the intermediate zone and weak or absent in differentiated neurons, whereas HuB and HuC have different distributions. (LLM, conf=0.94)

  cites Okano and Darnell 1997 source

In the paper

“Interestingly, a microarray screen of HuD-bound mRNAs found that less than half of its targets contain an ARE (Bolognani et al. 2010).”

What the sources say

• Supported

  The Methods describe microarray analysis of HuD-bound mRNAs. In Results, the authors report that only 42.48% of HuD targets had any of the known instability motifs examined, a group that includes AREs; thus fewer than half had an ARE. (LLM, conf=0.92)

  cites Bolognani et al. 2010 source

In the paper

“Recent high-throughput analyses, using variations of cross-linking and immunoprecipitation (CLIP) such as Photoactivatable-Ribonucleoside-Enhanced CLIP (PAR-CLIP) and individual-nucleotide resolution CLIP (iCLIP), of HuR and nELAV target mRNAs corroborate these findings by demonstrating that all four Hu proteins preferentially bind U-rich sequences interspersed with Gs or As (Lebedeva et al. 2011;”

What the sources say

• Partly supported

  The section “PAR-CLIP reproducibly recovers in vitro HuR motifs” reports abundant HuR-binding motifs that are U-rich, including sequences containing A or G. The Introduction says HuB, HuC and HuD bind U-rich elements, but this paper’s high-throughput motif analysis is of HuR; it does not demonstrate the stated G- or A-interspersed preference for all four Hu proteins. (LLM, conf=0.88)

  cites Lebedeva et al. 2011 sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section ('HuR-RNA interactions and RNA Recognition Element'; page unavailable) reports a PAR-CLIP analysis of HuR and identifies U-rich motifs interrupted by A or C. The Introduction describes uridine stretches separated by adenosines or, less commonly, other bases. This paper does not demonstrate the stated preference for Gs or As across all four Hu proteins; its high-throughput analysis examines HuR. (LLM, conf=0.87)

  cites Mukherjee et al. 2011 sourceExperimental — accuracy not yet measured
• Partly supported

  The Results and Discussion section reports iCLIP evidence that HuR binding sites are enriched for U-rich sequences. It does not report binding preferences for HuB, HuC, or HuD, or establish that Gs or As are interspersed in the preferred sequences. (LLM, conf=0.86)

  cites Uren et al. 2011 sourceExperimental — accuracy not yet measured

In the paper

“The same report also used genome wide analysis to map the binding sites in nELAV targeted pre-mRNAs and revealed that these proteins preferentially bind introns surrounding cassette exons, especially near exon/intron splice junctions (Ince-Dunn et al. 2012).”

What the sources say

• Supported

  The Results section (“Generation of nElavl-RNA regulatory map”) reports that, for the analyzed cassette exons, nElavl binding sites were usually in flanking introns and were most concentrated at exon/intron splice junctions. It also describes the genome-wide binding analysis used to build that map. (LLM, conf=0.94)

  cites Ince-Dunn et al. 2012 source

In the paper

“Once bound to a target mRNA, destabilizing RBPs may promote deadenylation through a variety of manners such as blocking poly(A) binding protein (PABP) binding and/or recruitment of decapping, deadenylation, and exosome components (Wu and Brewer 2012).”

What the sources say

• Partly supported

  Section 4.1 says AUF1 may prevent PABP from binding poly(A), allowing deadenylases access, and that KSRP, TTP, and BRF1 interact with deadenylation, decapping, and exosome factors. It describes those recruited factors as promoting mRNA degradation overall, however, and places exosome-mediated degradation after deadenylation; it does not say that recruiting decapping or exosome components promotes deadenylation itself. (LLM, conf=0.83)

  cites Wu and Brewer 2012 sourceExperimental — accuracy not yet measured

In the paper

“Truncation of the mouse HuB protein revealed that all three RRMs are necessary for Hu proteins to perform this function (Zhu et al. 2006).”

What the sources say

• Partly supported

  The Results report that Hu proteins regulate alternative processing of calcitonin/CGRP RNA and that a mouse HuC construct containing RRM3 and the hinge domain disrupted CGRP production, whereas an RRM1–RRM2 construct did not significantly affect exon inclusion. These experiments do not establish that all three RRMs are necessary for alternative polyadenylation, and the tested truncations were of mouse HuC, not mouse HuB. The cited copy provides no page numbers for these passages. (LLM, conf=0.86)

  cites Zhu et al. 2006 sourceExperimental — accuracy not yet measured

In the paper

“In addition to alternative splicing, both the Drosophila ELAV and the mammalian Hu proteins were demonstrated to control alternative polyadenylation specifically in neurons (Soller and White 2003).”

What the sources say

• Partly supported

  The Discussion reports that Drosophila ELAV inhibits 3′-end formation at an intronic polyadenylation site, promoting neuronal splicing of ewg. The paper does not demonstrate the same control by mammalian Hu proteins; its introductory passage instead describes their previously assigned functions as cytoplasmic RNA processing. (LLM, conf=0.89)

  cites Soller and White 2003 sourceExperimental — accuracy not yet measured

In the paper

“In vitro transcription elongation assays showed that, by blocking HDAC2 activity, histones surrounding specific exons remained hyperacetylated, which resulted in an increased RNAPII transcription rate and decreased exon inclusion at these genomic loci.”

What the sources say

• Partly supported

  The Discussion (page unavailable) proposes that Hu proteins inhibit HDAC2, sustaining local histone hyperacetylation and increasing RNAPII elongation; the elongation-rate Results report decreased Nf1 exon 23a inclusion with HuC expression. But the claim misidentifies the evidence as in vitro transcription elongation assays: the in vitro assay measured HDAC2 activity, while elongation was measured in cells. The full causal chain is presented as a proposed mechanism, not as the result of one assay. (LLM, conf=0.88)

  cites Zhou et al. 2011 sourceExperimental — accuracy not yet measured

In the paper

“For instance, all four Hu members were shown to promote inclusion of HuD exon 6 by binding to two ARE sequences in the downstream intron (Wang et al. 2010).”

What the sources say

• Supported

  The Results section reports testing all four Hu family members for promotion of HuD exon 6 inclusion. The Results identify two downstream AU-rich elements important for that effect and show HuC binding to them; the Discussion describes Hu-mediated inclusion as occurring through binding to those downstream sequences. Page numbers are unavailable in our copy. (LLM, conf=0.92)

  cites Wang et al. 2010 source

In the paper

“Among all of the HuD-regulated mRNAs, the most prominent is the GAP-43 mRNA, which houses a class III ARE in its 3′ UTR (Chung et al. 1997; Tsai et al. 1997).”

What the sources say

• Partly supported

  The paper describes a conserved U-rich element in the GAP-43 mRNA 3′ UTR and maps a 26-nucleotide HuD-binding site there (Abstract; HuD binding-site section, page unavailable). Our copy does not identify that element as a class III ARE, so the specific classification is not established by this source. (LLM, conf=0.84)

  cites Chung et al. 1997 sourceExperimental — accuracy not yet measured
• Partly supported

  The Discussion (page not available) says the GAP-43 3′ UTR contains sequences resembling AU-rich elements, and the section on cis-acting elements identifies a U-rich instability determinant there. Our copy does not classify that element as a class III ARE, so it supports the location and general type of element but not the specific classification. (LLM, conf=0.82)

  cites Tsai et al. 1997 sourceExperimental — accuracy not yet measured

In the paper

“Moreover, all four Hu proteins were recently demonstrated to differentially regulate alternative polyadenylation of HuR in neurons (Mansfield and Keene 2011; also see Dai et al. 2012).”

What the sources say

• Partly supported

  The Introduction (page unavailable) says all four Hu proteins can drive alternative polyadenylation of HuR mRNA to produce a neuron-specific isoform. However, the regulation experiments were conducted in HEK293T cells, not neurons, and the Discussion describes the proteins’ differing efficiencies as an observation that remains to be rigorously tested. The source therefore does not establish that all four differentially regulate HuR polyadenylation in neurons. (LLM, conf=0.86)

  cites Mansfield and Keene 2011 sourceExperimental — accuracy not yet measured
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Dai et al. 2012

In the paper

“In addition to binding intronic sequences, co-IP assays revealed that Hu proteins interact with RNA polymerase II and histone deacetylase 2 (HDAC2) to regulate alternative splicing (Zhou et al. 2011).”

What the sources say

• Supported

  The section “Hu Proteins Associate with Transcriptionally Active RNAPII in Neuronal…” reports reciprocal co-IP evidence that HuR associates with RNA polymerase II and further co-IP evidence for other Hu family members. “Hu Proteins Directly Interact with Histone Deacetylase 2” reports a co-IP-confirmed interaction with HDAC2. The Discussion links these interactions to the proposed mechanism of alternative-splicing regulation; page numbers were not available in our copy. (LLM, conf=0.94)

  cites Zhou et al. 2011 source

In the paper

“Furthermore, overexpression and down-regulation of HuD in T-cell lines demonstrated that it mediates alternative splicing of the Ikaros gene, possibly by suppressing exon 4 inclusion (Bellavia et al. 2007; Hinman and Lou 2008).”

What the sources say

• Partly supported

  The section on HuD-dependent IK variants and Figure 6 report that HuD overexpression in T-cell lines increased short Ikaros dominant-negative isoforms, while HuD knockdown prevented Notch3-induced changes in those isoforms. The paper also identifies an exon-4-lacking Ikaros isoform, but does not establish that HuD specifically suppresses exon 4 inclusion; it leaves open effects on splicing and/or RNA stability. (LLM, conf=0.84)

  cites Bellavia et al. 2007 sourceExperimental — accuracy not yet measured
• Supported

  The “Ikaros isoforms” section reports that HuD overexpression and siRNA knockdown in pre- and immature T-cell lines changed the formation of alternatively spliced Ikaros isoforms. It proposes that HuD may block exon 4 inclusion, while stating that direct involvement in that splicing control remains unproven. Page numbers were not supplied. (LLM, conf=0.91)

  cites Hinman and Lou 2008 source

In the paper

“Using various complementary methods, such as REMSA and UV cross-linking/IP assays, one report demonstrated that nELAVs compete with TIA-1/TIAR RBPs for a U-rich intronic sequence in the calcitonin/calcitonin gene-related peptide (CGRP) pre-mRNA to block inclusion of exon 4. Through this mechanism, nELAVs promote expression of the neuron-specific CGRP isoform in neurons (Zhu et al. 2006).”

What the sources say

• Supported

  The Discussion states that Hu proteins compete with TIA-1/TIAR for the same intronic U-tract in calcitonin/CGRP pre-mRNA, blocking proteins that promote exon 4 inclusion. The Introduction explains that skipping exon 4 produces the neuron-specific CGRP pathway. The paper reports this mechanism in neuron-like cells. (LLM, conf=0.93)

  cites Zhu et al. 2006 source

In the paper

“Experiments with HuB and HuC deletion mutants indicated that the linker region and RRM3 are necessary for nELAV regulation of alternative splicing (Zhu et al. 2008; Zhou et al. 2011).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Zhu et al. 2008
• Partly supported

  The section ‘Hu Proteins Associate with Transcriptionally Active RNAPII in Neuronal’ reports that deleting RRM3 or the hinge domain reduced HuC’s interaction with RNAPII. It does not establish that these regions are necessary for nELAV regulation of alternative splicing, or report the claimed HuB and HuC deletion-mutant splicing result. No page number was available for the passage. (LLM, conf=0.82)

  cites Zhou et al. 2011 sourceExperimental — accuracy not yet measured

In the paper

“Mansfield and Keene showed that there are three different HuR mRNA polyadenylation variants (1.5, 2.4, and 6.0 kb), which differ in 3′ UTR length.”

What the sources say

• Supported

  The Introduction states that HuR mRNA has three isoforms arising through alternative polyadenylation, identifies them as 1.5, 2.4, and 6.0 kb, and says they differ in 3′-UTR length. (LLM, conf=0.95)

  cites Mansfield and Keene 2011 source

In the paper

“All four Hu members were found to bind and block U-rich sequences near the 2.4-kb polyadenylation site and thereby promote expression of the 6.0-kb transcript.”

What the sources say

• Partly supported

  The Results report that all four Hu proteins bind near the 2.4-kb polyadenylation site and that Hu-protein overexpression increases the 6.0-kb HuR transcript. But the Results describe interference with polyadenylation as potential and say they could not definitively prove a direct effect. The claim overstates the evidence by saying all four were found to block the site and thereby promote the longer transcript. (LLM, conf=0.90)

  cites Mansfield and Keene 2011 sourceExperimental — accuracy not yet measured

In the paper

“On the other hand, the study by Lee et al. showed that the repression of Ins2 translation by HuD is likely required to maintain insulin homeostasis (Lee et al. 2012).”

What the sources say

• Supported

  The Results report that HuD represses Ins2 mRNA translation. The Discussion proposes that this negative regulation balances stimulation of insulin production, helping restore insulin to homeostatic levels. The claim’s “likely required” wording is consistent with that proposed role; page numbers are not provided in our copy. (LLM, conf=0.92)

  cites Lee et al. 2012 source

In the paper

“In addition to enhancing translation, HuD is capable of repressing protein synthesis, as shown for p27 and preproinsulin (Ins2) mRNAs (Kullmann et al. 2002; Lee et al. 2012).”

What the sources say

• Supported

  The Results report that HuD overexpression inhibited translation of a reporter bearing the p27 5′UTR and sharply reduced its IRES activity. Kullmann et al. support the p27 part of the sentence; the separate Ins2 example is paired with Lee et al. (2012), not this source. (LLM, conf=0.94)

  cites Kullmann et al. 2002 source
• Supported

  The Discussion states that HuD represses p27 translation, citing Kullmann et al. (2002). The Results independently show that HuD reduces Ins2 mRNA translation and proinsulin production. No page numbers are provided in our copy. (LLM, conf=0.94)

  cites Lee et al. 2012 source

In the paper

“Fluorescence resonance energy transfer (FRET) and biochemical techniques revealed that HuR interacts with AUF1, KSRP, and TIA-1 in the nucleus and cytoplasmic stress granules (David et al. 2007; David Gerecht et al. 2010).”

What the sources say

• Partly supported

  The section on FRET-detected complexes reports a HuR–p37AUF1 interaction in the nucleus. But the stress-granule section says HuR colocalizes with TIA-1 while AUF1 does not enter the granules; colocalization does not establish an interaction with TIA-1. The paper mentions KSRP but does not report a HuR–KSRP interaction. Page numbers are unavailable in our copy. (LLM, conf=0.90)

  cites David et al. 2007 sourceExperimental — accuracy not yet measured
• Supported

  The Results section reports FRET evidence of HuR–AUF1 contact in both the nucleus and stress granules (passage 6). It also reports HuR–KSRP and HuR–TIA-1 interactions in both locations (passage 1), in arsenite-treated cells. (LLM, conf=0.94)

  cites David Gerecht et al. 2010 source

In the paper

“Currently, there are only three known pathways that regulate the abundance or function of HuD: protein kinase C (PKC) (Mobarak et al. 2000; Pascale et al. 2005; Lim and Alkon 2012); coactivator-associated arginine methyltransferase 1 (CARM1) (Fujiwara et al. 2006; Hubers et al. 2010); and protein kinase B (PKB/AKT) (Fujiwara et al. 2011a).”

What the sources say

• Partly supported

  The Mobarak et al. citation is attached to the PKC pathway, not to CARM1 or PKB/AKT. The Discussion says PKC likely controls HuD function, but presents this as an inference rather than an established regulatory pathway; its experiments establish HuD’s role in PKC-dependent neurite outgrowth in PC12 cells. (LLM, conf=0.83)

  cites Mobarak et al. 2000 sourceExperimental — accuracy not yet measured
• Supported

  The citation to Fujiwara et al. is attached to CARM1, not to the PKC or PKB/AKT pathways. The Abstract reports that CARM1 methylates HuD in PC12 cells and that this changes HuD’s binding to p21 mRNA, supporting CARM1 as a regulator of HuD function. (LLM, conf=0.94)

  cites Fujiwara et al. 2006 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Fujiwara et al. 2011a

In the paper

“The ability of HuD to control these early differentiation processes requires post-transcriptional regulation of specific target transcripts such as mRNAs encoding cyclin-dependent kinase p21cip1/waf1 (Fujiwara et al. 2006).”

What the sources say

• Partly supported

  The Results show that HuD protects p21cip1/waf1 mRNA from decay, and the paper links reduced HuD methylation with slower growth and neurite outgrowth in PC12 cells. But the Discussion describes HuD’s protective effect on differentiation-related transcripts as presumed; it does not establish that regulation of p21cip1/waf1 is required for HuD to control early differentiation. (LLM, conf=0.82)

  cites Fujiwara et al. 2006 sourceExperimental — accuracy not yet measured

In the paper

“illustrating in vivo the importance of HuD for inhibition of neuronal stem/progenitor cell self-renewal (Akamatsu et al. 2005).”

What the sources say

• Supported

  The Results report increased self-renewal activity in neural stem/progenitor cells from fetal and adult HuD-deficient mice. The Conclusion interprets the loss-of-function findings as showing that HuD negatively regulates these cells' proliferation, supporting the cited in vivo point. Page numbers were not supplied. (LLM, conf=0.92)

  cites Akamatsu et al. 2005 source

In the paper

“Studies in which HuD levels were down-regulated or over-expressed in cultured cells have revealed an essential role for HuD in terminal differentiation, namely dendritic and axonal outgrowth (Wakamatsu and Weston 1997; Aranda-Abreu et al. 1999; Mobarak et al. 2000; Anderson et al. 2001; Hubers et al. 2010).”

What the sources say

• ?Not checked — no full text of the sourcecites Wakamatsu and Weston 1997 source
• Partly supported

  The section on r-HuD antisense treatment reports that reducing HuD caused neurite retraction in NGF-treated PC12 cells, supporting a role in neurite outgrowth. The Discussion explicitly says this model produces neurite extension, not defined dendrites and axons, so this paper does not establish the claim's more specific dendritic and axonal outgrowth. Page numbers were not provided for these passages. (LLM, conf=0.90)

  cites Aranda-Abreu et al. 1999 sourceExperimental — accuracy not yet measured
• Partly supported

  The Results and Discussion show that reducing HuD impairs NGF- and PKC-dependent neurite outgrowth in PC12 cells, while overexpressing HuD promotes process outgrowth. But the study examines early, immature neurites rather than establishing an essential role in terminal differentiation or specifically in both dendritic and axonal outgrowth; cAMP-dependent outgrowth remains intact. Page numbers are not available in our copy. (LLM, conf=0.88)

  cites Mobarak et al. 2000 sourceExperimental — accuracy not yet measured

In the paper

“Adult HuD−/− mice were also found to contain an increased number of self-renewing cells in the subventricular zone (SVZ), illustrating in vivo the importance of HuD for inhibition of neuronal stem/progenitor cell self-renewal (Akamatsu et al. 2005).”

What the sources say

• Supported

  The Results report 1.5- to 2.0-fold more BrdUrd-positive cells in the adult SVZ of HuD−/− mice than in wild-type littermates (Fig. 5). The Results also interpret the adult SVZ findings as evidence of increased neural stem/progenitor-cell self-renewal. No page numbers are provided in our copy. (LLM, conf=0.94)

  cites Akamatsu et al. 2005 source

In the paper

“Indeed, analysis of HuD-targeted mRNAs in the mouse forebrain showed that HuD binds to its own transcript, although the role of this interaction remains unknown (Bolognani et al. 2010).”

What the sources say

• Supported

  The Discussion explicitly states that HuD binds its own mRNA. The Results describe isolating HuD-bound mRNAs from the brains of HuD-overexpressing mice, whose increased neuronal HuD expression is identified as occurring in the forebrain. (LLM, conf=0.93)

  cites Bolognani et al. 2010 source

In the paper

“In support of these findings, transgenic mice ectopically expressing HuD (HuD-Tg) in forebrain neurons under the control of the CAMKIIα promoter (Bolognani et al. 2007b) were shown to contain increased mossy fiber length (Perrone-Bizzozero et al. 2011).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Bolognani et al. 2007b
• Supported

  The Animals section identifies HuD-Tg mice as expressing HuD under the αCaMKII promoter. The Results section reports significantly increased relative length of the infrapyramidal mossy fibre bundle in those mice; the finding concerns that bundle, not every mossy fibre. (LLM, conf=0.92)

  cites Perrone-Bizzozero et al. 2011 source

In the paper

“whereas FoxO1 was recently found to negatively regulate transcription of HuD under low glucose conditions in pancreatic β cells (Lee et al. 2012).”

What the sources say

• Supported

  In Results, “HuD is expressed in pancreatic β cells” (Fig. 1I–L), the paper identifies FoxO1 as a transcriptional repressor, reports greater FoxO1 association with the HuD promoter under low glucose, and shows that FoxO1 silencing increases HuD expression while overexpression reduces it. Together, these findings support the attributed negative regulation in pancreatic β cells. (LLM, conf=0.94)

  cites Lee et al. 2012 source

In the paper

“These variants encode transcripts exhibiting unique temporal expression during Xenopus nervous system development (Nassar 2011).”

What the sources say

• Supported

  The Abstract reports that elrD1 and elrD2 have the same tissue-specific expression pattern but distinct developmental regulation. The ‘Expression of elrD1 and elrD2 transcripts’ section reports that their relative abundance changes across developmental stages, supporting the claim about distinct temporal expression during Xenopus neural development. (LLM, conf=0.91)

  cites Nassar 2011 source

In the paper

“Also of particular relevance is the possible role of HuD in spinal muscular atrophy (SMA), a disease that results in degeneration of spinal cord motor neurons due to deletion or loss-of-function mutations in the survival of motor neuron 1 (SMN1) gene, resulting in inadequate expression of functional SMN protein (Burghes and Beattie 2009).”

What the sources say

• Partly supported

  The Introduction and Abstract support the sentence’s description of SMA as a motor-neuron disorder caused by loss or mutation of SMN1 and reduced SMN protein. Our copy does not mention HuD or propose a role for it in SMA (searched: HuD, ELAVL4), so it does not support that part of the claim. (LLM, conf=0.84)

  cites Burghes and Beattie 2009 sourceExperimental — accuracy not yet measured

In the paper

“The first studies to link HuD to learning and memory demonstrated that expression of nELAV proteins and GAP-43 mRNA increased in the cytoskeletal and membrane fractions of murine hippocampal neurons following spatial discrimination tasks (Quattrone et al. 2001; Pascale et al. 2004).”

What the sources say

• Partly supported

  The Results and Discussion report increased neuronal ELAV-like protein in the membrane and especially cytoskeletal fractions of hippocampi from radial-maze-trained mice. They also report learning-associated up-regulation of GAP-43 mRNA, but do not show that its increase occurred in those fractions; the fraction-specific finding concerns the proteins. (LLM, conf=0.88)

  cites Quattrone et al. 2001 sourceExperimental — accuracy not yet measured
• Partly supported

  The Discussion reports earlier up-regulation of neuronal ELAV proteins after a mouse spatial task, while this paper's Results examine rats trained in the Morris water maze. The Results show increased ELAV-like proteins chiefly in the cytoskeletal fraction and increased GAP-43 mRNA in the hippocampus. The membrane and cytoskeletal fraction increases reported for GAP-43 concern its protein, not its mRNA; the ELAV-like protein increase had no membrane contribution. (LLM, conf=0.89)

  cites Pascale et al. 2004 sourceExperimental — accuracy not yet measured

In the paper

“In accordance with its direct or indirect function in learning and memory, nELAVs have recently been linked to Alzheimer’s disease (AD), a condition characterized by neuronal death, memory loss and eventual dementia.”

What the sources say

• Supported

  The Results section, ‘The nELAV are decreased in postmortem AD patients,’ reports that nELAV levels decreased with clinical dementia progression in AD patients. The Discussion likewise describes nELAV proteins as affected in AD pathology, directly supporting the stated link. (LLM, conf=0.95)

  cites Amadio et al. 2009 source

In the paper

“Furthermore, as mentioned above, microarray analysis of HuD-targeted mRNAs in DGCs demonstrated that HuD-Tg mice contained increased expression of transcripts whose products regulate neuronal development and axogenesis (Perrone-Bizzozero et al. 2011).”

What the sources say

• Supported

  The Results sections on mRNA profiling and GO analysis report that microarrays found increased transcripts in HuD-Tg dentate granule cells and that the up-regulated set was enriched for genes involved in neural development and axonogenesis. The GO analysis identifies regulators of axogenesis and neuronal differentiation among them; our copy does not provide page numbers for these passages. (LLM, conf=0.93)

  cites Perrone-Bizzozero et al. 2011 source

In the paper

“Additionally, HuD has been implicated in axonal regeneration in two models of nerve injury.”

What the sources say

• Supported

  The Discussion describes a putative role for HuD in regeneration after axotomy in motoneurons and sensory neurons—two nerve-injury models. It reports elevated HuD during the regenerative phase and also presents the paper’s own findings after SCG axotomy. (LLM, conf=0.93)

  cites Deschenes-Furry et al. 2007 source
• ?Not checked — no full text of the sourcecites Anderson et al. 2003 source

In the paper

“Importantly, the reduction in AChE mRNA abundance could be rescued by localized overexpression of HuD delivered via a viral vector.”

What the sources say

• Supported

  The section ‘Exogenous expression of HuD maintains AChE mRNA levels after axotomy’ reports that a HuD-carrying HSV was injected into rat superior cervical ganglia before axotomy. AChE mRNA fell after axotomy in controls but remained at sham-operated levels when HuD was expressed; Figure 7 describes this as a rescue. (LLM, conf=0.94)

  cites Deschenes-Furry et al. 2007 source

In the paper

“In parallel with this potential role, studies have demonstrated that HuD protein levels, as well as a cohort of its target mRNAs such as GAP-43, CAMKIIα and Homer, increase in several brain regions including the dentate gyrus (DG) following neurotoxin-induced seizure (Bolognani et al. 2007a; Tiruchinapalli et al. 2008a; Winden et al. 2011).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Bolognani et al. 2007a
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Tiruchinapalli et al. 2008a
• Partly supported

  The Results (‘Mechanisms of neuronal response to seizures’; page not available) report increased HuD expression by qRT-PCR in both hemispheres of animals with chronic seizures and an association between HuD target genes and seizures. The paper uses a kainic-acid seizure model focused on the hippocampus and dentate gyrus, but these passages do not establish increased HuD protein levels, increases in the named target mRNAs, or increases across several brain regions. (LLM, conf=0.89)

  cites Winden et al. 2011 sourceExperimental — accuracy not yet measured

In the paper

“Importantly, overexpression of HuD or of one of its target mRNAs (cpg-15) was found to partially rescue SMA-like defects related to cell morphology and recruitment of specific mRNAs into RNA granules (Hubers et al. 2010; Akten et al. 2011).”

What the sources say

• ?Not checked — no full text of the sourcecites Hubers et al. 2010 source
• Partly supported

  The Results (page not specified) report that cpg15 mRNA overexpression partially rescued motor-axon defects in SMN-deficient zebrafish, supporting the morphology portion of the claim. The paper identifies HuD as an SMN-interacting protein but does not report rescue by HuD overexpression or rescue of mRNA recruitment into RNA granules. (LLM, conf=0.86)

  cites Akten et al. 2011 sourceExperimental — accuracy not yet measured

In the paper

“Conversely, detailed analysis of HuD−/− mice revealed a transient impairment in neurite extension of several cranial nerves around day 10.5 of embryonic development (Akamatsu et al. 2005).”

What the sources say

• Supported

  The Results report impaired neurite extension in several named cranial nerves of most HuD−/− embryos at E10.5. The same passage says the developmental delay was absent in later-stage embryos, supporting the description as transient. (LLM, conf=0.95)

  cites Akamatsu et al. 2005 source

In the paper

“A series of cell imaging and biochemical experiments in three independent studies demonstrated that HuD interacts with SMN protein in axonal compartments of neurons (Hubers et al. 2010; Akten et al. 2011; Fallini et al. 2011).”

What the sources say

• ?Not checked — no full text of the sourcecites Hubers et al. 2010 source
• Supported

  The Results (Fig. 1C–F) report reciprocal co-immunoprecipitation of SMN and HuD and their colocalization in motor-neuron axons. The Discussion likewise identifies HuD as strongly associated with SMN in motor-neuron axons. (LLM, conf=0.94)

  cites Akten et al. 2011 source
• Supported

  The Introduction reports that SMN and HuD colocalize in actively transported axonal granules, and the Results section on SMN–HuD interaction reports biochemical assays demonstrating their association. The copy provides no page numbers for these passages. (LLM, conf=0.94)

  cites Fallini et al. 2011 source

In the paper

“The authors also determined that the interaction between nELAV proteins and ADAM10 mRNA was disrupted following exposure to Aβ1–42 leading to reduced ADAM10 protein levels (Amadio et al. 2009).”

What the sources say

• Partly supported

  The Results report that Aβ1–42 exposure disrupted detectable nELAV–ADAM10 mRNA binding and reduced ADAM10 protein levels. The Discussion says the reduced protein expression may result from disrupted binding, but notes that post-translational effects cannot be excluded. Thus, the causal link implied by “leading to” is stronger than the paper establishes (page numbers not supplied). (LLM, conf=0.86)

  cites Amadio et al. 2009 sourceExperimental — accuracy not yet measured

In the paper

“A third study assessed gene expression using microarray platforms to show that HuD and several of its target mRNAs increased following kainic acid-induced seizures in rats (Winden et al. 2011).”

What the sources say

• Supported

  The Methods (Animals; page not provided) describe kainic-acid injection in Wistar rats followed by seizure monitoring and microarray analysis. The Results (Mechanisms of neuronal response to seizures; page not provided) report higher HuD expression in rats with seizures and significant enrichment of upregulated HuD target genes. (LLM, conf=0.92)

  cites Winden et al. 2011 source

In the paper

“Importantly, using a combination of promoter-reporter assays, chromatin IPs, and electrophoretic mobility shift assays, we showed that Ngn2 binds these two E-boxes to promote expression of HuD only in cells differentiating into neurons.”

In the paper

“Moreover, our data suggest that E1c is the predominantly expressed E1 variant (Bronicki et al. 2012).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Bronicki et al. 2012

In the paper

“Work in our laboratory has shown that the mammalian HuD gene actually contains eight E1 variants that are well conserved among higher vertebrates, adding to the speculation that multiple promoters control HuD expression (Bronicki et al. 2012).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Bronicki et al. 2012

In the paper

“We also found that most E1 variants house an in-frame methionine codon (with the exception of E1a4, since it harbors two stop codons downstream from the AUG), suggesting that they may encode alternate HuD N termini.”

In the paper

“The combinatorial complexity of HuD alternative 5′ and 3′ exons may produce up to 24 different mRNA variants.”

In the paper

“Another function of the third RRM of HuD involves interacting with other proteins, including homo- and hetero-multimerizing with Hu members (Kasashima et al. 2002).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Kasashima et al. 2002

In the paper

“At the subcellular level, HuD is predominantly expressed in the cytoplasm, with minor levels detected in the nucleus (Kasashima et al. 1999).”

What the sources say

• ?Not checked — no full text of the sourcecites Kasashima et al. 1999 source

In the paper

“Closer inspection of intraneuronal compartments revealed that HuD is localized to granules, along with other proteins, such as kinesin-like protein (KIF3A) and survival of motoneuron (SMN), within the cytoplasm and neurites (Aronov et al. 2002; Smith et al. 2004; Tiruchinapalli et al. 2008a,b; Hubers et al. 2010; Akten et al. 2011; Fallini et al. 2012b).”

What the sources say

• ?Not checked — no full text of the sourcecites Aronov et al. 2002 source
• ?Not checked — no full text of the sourcecites Smith et al. 2004 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Tiruchinapalli et al. 2008a,b

In the paper

“This report also showed that the amino acid residues interacting with RNA nucleotides are well conserved among all Hu proteins and the Drosophila ELAV protein.”

What the sources say

• ?Not checked — no full text of the sourcecites Wang and Tanaka Hall 2001 source

In the paper

“The crystal structure of HuD bound to c-fos or tumor necrosis factor α (TNFα) mRNAs illustrates that specific residues within its first two RRMs preferentially bind the pyrimidine-rich X-U/C-U-X-X-U/C?-U-U/C consensus sequence where the “?” denotes ambiguity whether a cytosine in this position is tolerated (Wang and Tanaka Hall 2001).”

What the sources say

• ?Not checked — no full text of the sourcecites Wang and Tanaka Hall 2001 source

In the paper

“Altogether, these studies clearly demonstrate that HuD, along with the other nELAV proteins, can promote or suppress exon inclusion by interacting with (or antagonizing) splicing, transcription, and chromatin components (Fig. 2A).”

In the paper

“Since these initial findings, HuD has emerged as the best-described stabilizing RBP in neurons, as evidenced by the numerous studies outlining its role in increasing the half-lives of various neuronal transcripts (Fig. 2C).”

In the paper

“Using REMSAs, the authors showed that HuD binds specifically to an ARE sequence in the c-fos 3′ UTR.”

What the sources say

• ?Not checked — no full text of the sourcecites Liu et al. 1995 source

In the paper

“One likely mechanism through which HuD and other Hu members stabilize mRNAs involves antagonizing destabilizing RBPs such as AUF1 from binding to cis-acting elements (Barreau et al. 2006).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Barreau et al. 2006

In the paper

“Overexpression of wild-type and deletion mutant HuD proteins revealed that cytoplasmic shuttling of HuD requires the NES region (Kasashima et al. 1999).”

What the sources say

• ?Not checked — no full text of the sourcecites Kasashima et al. 1999 source

In the paper

“As previously mentioned, HuD contains a NES and putative NLS located in the variable linker domain, between the second and third RRM, which permit nucleocytoplasmic shuttling of HuD (Fig. 2B; Kasashima et al. 1999).”

What the sources say

• ?Not checked — no full text of the sourcecites Kasashima et al. 1999 source

In the paper

“Numerous other ARE-harboring transcripts, such as N-myc and c-myc, were later identified as targets of HuD using similar in vitro approaches, indicating that HuD binds short-lived mRNAs whose protein product functions in cell proliferation (Liu et al. 1995; Ross et al. 1997).”

What the sources say

• ?Not checked — no full text of the sourcecites Liu et al. 1995 source
• ?Not checked — no full text of the sourcecites Ross et al. 1997 source

In the paper

“Complementary to its role in mRNA localization, evidence for the direct involvement of HuD in regulating translation was unveiled when Fukao and colleagues showed that HuD binds to eIF4A and the poly(A) tail of transcripts, via its linker region and third RRM, to enhance cap-dependent protein synthesis (Fukao et al. 2009).”

What the sources say

• ?Not checked — no full text of the sourcecites Fukao et al. 2009 source

In the paper

“This study clearly illustrates that PKC activation negatively controls CARM1-mediated methylation of HuD to promote neuronal differentiation.”

In the paper

“The phosphatidylinositol 3-kinase (PI3K)/AKT1 pathway was also found to regulate HuD function, specifically at the translational level (Fujiwara et al. 2011a).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Fujiwara et al. 2011a

In the paper

“Furthermore, activating the classical PKC isoforms and simultaneously blocking CARM1 activity potentiates HuD binding to target mRNAs and hippocampal neurite extension.”

What the sources say

• ?Not checked — no full text of the sourcecites Lim and Alkon 2012 source

In the paper

“suggesting that AKT1 also positively controls HuD expression”

In the paper

“In hippocampal neurons, the study demonstrated using pathway-specific inhibitors that activated PKC isoforms interact and phosphorylate CARM1, which leads to decreased CARM1 methyltransferase activity.”

What the sources say

• ?Not checked — no full text of the sourcecites Lim and Alkon 2012 source

In the paper

“In addition to binding HuD, chronic (7-day) activation of AKT1 enhances HuD protein levels, suggesting that AKT1 also positively controls HuD expression (Tiruchinapalli et al. 2008a).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Tiruchinapalli et al. 2008a

In the paper

“suggesting that stabilization of these other target mRNAs requires additional post-translational modifications of HuD and/or other trans-acting factors”

In the paper

“For example, two target mRNAs of HuD involved in axonal outgrowth, namely GAP-43 and Tau, were found to colocalize with HuD protein and polysomes in growth cones during neuronal differentiation (Smith et al. 2004; Atlas et al. 2007).”

What the sources say

• ?Not checked — no full text of the sourcecites Smith et al. 2004 source
• ?Not checked — no full text of the sourcecites Atlas et al. 2007 source

In the paper

“However, there is evidence indicating that this mechanism is more complex since both stabilizing and destabilizing RBPs can bind the same transcript simultaneously.”

In the paper

“Moreover, this mechanism was determined to be important for HuD- dependent neurite extension in PC12 cells.”

What the sources say

• ?Not checked — no full text of the sourcecites Fukao et al. 2009 source

In the paper

“Co-IP and immunocytochemistry experiments revealed that HuD interacts with a host of mRNP components involved in transport and translation in the cytoplasm and neurites such as the motor protein KIF3A (Aronov et al. 2002), IGF-II mRNA binding protein 1 (IMP-1) (Atlas et al. 2004, 2007), survival of motor neuron (SMN) (Hubers et al. 2010; Akten et al. 2011; Fallini et al. 2011), poly(A) binding”

What the sources say

• ?Not checked — no full text of the sourcecites Aronov et al. 2002 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Atlas et al. 2004, 2007
• ?Not checked — no full text of the sourcecites Hubers et al. 2010 source

In the paper

“Analysis of the Xenopus HuD homolog elrD sequence illustrated that the 3′ UTR contains an ∼100-nt stretch of nucleotides with 90% identity to the human HuD 3′ UTR, implying that this fragment encompasses an important evolutionarily conserved regulatory structure and/or cis-element(s) (Good 1995).”

What the sources say

• ?Not checked — no full text of the sourcecites Good 1995 source

In the paper

“This auto-regulatory mechanism is thought to occur when ELAV levels pass a certain threshold, resulting in increased ELAV binding to an AU-rich site in a noncoding 3′-terminal exon and production of a noncoding transcript (Borgeson and Samson 2005).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Borgeson and Samson 2005

In the paper

“Given the established function of Ngn2 in neurogenesis (Guillemot 2007) and its emerging roles in learning and memory (Galichet et al. 2008) and neuronal diseases (Rostomily et al. 1997; Andersson et al. 2006; Kele et al. 2006; Uhrig et al. 2009), our findings suggest that Ngn2-dependent control of HuD transcription is central to neuronal development, function, and dysfunction (Fig. 4D).”

What the sources say

• ?Not checked — no full text of the sourcecites Guillemot 2007 source
• ?Not checked — no full text of the sourcecites Galichet et al. 2008 source
• ?Not checked — no full text of the sourcecites Rostomily et al. 1997

In the paper

“implying that the developmental regulation and function of these two mammalian exons is evolutionarily conserved”

In the paper

“Altogether, these studies stress that HuD transcripts are likely subjected to intricate post-transcriptional control involving RBPs and miRs.”

In the paper

“In line with this possibility, the 5′ genomic region of elrD was demonstrated to contain two distinct promoters that drive neuron-specific expression of two E1 variants, E1 and E′1 (Nassar and Wegnez 2001).”

What the sources say

• ?Not checked — no full text of the sourcecites Nassar and Wegnez 2001 source

In the paper

“The stability and translation of mature HuD mRNA is negatively controlled by miR-375 and potentially other trans-acting factors.”

In the paper

“The multiple post-transcriptional effects exerted by HuD on mRNAs whose proteins have key roles in neurons (Table 2) and its expansive spatiotemporal expression within the nervous system strongly suggest that HuD acts as a “master regulator” of various neuronal processes (Deschenes-Furry et al. 2006; Perrone-Bizzozero and Bird 2013).”

What the sources say

• ?Not checked — no full text of the sourcecites Deschenes-Furry et al. 2006 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Perrone-Bizzozero and Bird 2013

In the paper

“During neuronal development transcription of the HuD gene is positively regulated by the Ngn2-E47 heterodimer binding to E-boxes upstream of E1c.”

In the paper

“Research in our laboratory has revealed that the induction of HuD during early neuronal differentiation of P19 cells, a multipotent embryonal carcinoma cell line, is under neuron-specific transcriptional control (Bronicki et al. 2012).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Bronicki et al. 2012

In the paper

“Knockdown of miR-375 in cultured cells and mouse brain revealed that this microRNA prevents neurite outgrowth through negative control of HuD expression.”

What the sources say

• ?Not checked — no full text of the sourcecites Abdelmohsen et al. 2010 source

In the paper

“Multiple studies on primary and cultured neuronal cells have demonstrated that HuD controls almost all stages of a neuron’s existence, including neuronal commitment, differentiation, and activity (Deschenes-Furry et al. 2006; Pascale and Govoni 2012).”

What the sources say

• ?Not checked — no full text of the sourcecites Deschenes-Furry et al. 2006 source
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Pascale and Govoni 2012

In the paper

“Moreover, HuD-dependent neurogenesis requires commitment of cells to the neuronal lineage since ectopic expression of HuD in nonneuronal cells does not result in neuronal differentiation (Wakamatsu and Weston 1997).”

What the sources say

• ?Not checked — no full text of the sourcecites Wakamatsu and Weston 1997 source

In the paper

“To further study the role of HuD in learning and memory, HuD-Tg mice were employed since these mice express HuD throughout the forebrain, including the hippocampus and cerebral cortex (Bolognani et al. 2006).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Bolognani et al. 2006

In the paper

“These two studies provide a strong indication that the eventual up-regulation of endogenous HuD levels post-nerve injury may be involved in axonal recovery following nerve damage.”

In the paper

“Along with the finding that several HuD-targeted mRNAs encode synaptic proteins (Bolognani et al. 2010), these studies indicate that HuD is important for various types of neuronal plasticity, potentially by directly acting at the synapse.”

What the sources say

• Not checked yetcites Bolognani et al. 2010 source

In the paper

“In addition to its potential role in AD, three separate cohort genetic studies have linked single nucleotide polymorphisms (SNPs) within the HuD locus to the development of Parkinson’s disease (PD), a degenerative disorder of the CNS.”

What the sources say

• ?Not checked — no full text of the sourcecites Noureddine et al. 2005 source
• ?Not checked — no full text of the sourcecites Haugarvoll et al. 2007 source
• ?Not checked — no full text of the sourcecites DeStefano et al. 2008 source

In the paper

“Based on these findings, it was concluded that the precise spatiotemporal control of HuD levels is necessary for proper learning and memory.”

In the paper

“Last, a subsequent study employed samples from a Caucasian population to confirm that the rs967582 SNP is associated with increased risk of PD (DeStefano et al. 2008).”

What the sources say

• ?Not checked — no full text of the sourcecites DeStefano et al. 2008 source

In the paper

“Increasing evidence suggests that HuD also plays a role in different types of neuronal plasticity.”

In the paper

“Although HuD expression was shown to decrease immediately following nerve injury, another study performed nerve crush of dorsal root ganglion (DRG) neurons which resulted in an increase of HuD protein and GAP-43 mRNA expression within 7 d, lasting up to 21 d post-injury (Anderson et al. 2003).”

What the sources say

• ?Not checked — no full text of the sourcecites Anderson et al. 2003 source

In the paper

“Given its multiple important roles in neurons, it is not surprising that misregulation or misexpression of HuD is implicated in several neural pathologies and tumors (Pascale and Govoni 2012; Perrone-Bizzozero and Bird 2013).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Pascale and Govoni 2012
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Perrone-Bizzozero and Bird 2013

In the paper

“These studies provide a clear demonstration that HuD positively regulates neurite outgrowth.”

In the paper

“Closer inspection of HuD expression revealed increased HuD protein levels in somatic and dendritic compartments of hilar and CA3 hippocampal neurons following a different learning paradigm, contextual fear conditioning (Bolognani et al. 2004).”

What the sources say

• ?Not checked — no full text of the sourcecites Bolognani et al. 2004 source

In the paper

“Thus increases in HuD levels after nerve injury may facilitate regeneration.”

In the paper

“The first of these studies genotyped nine SNPs in the HuD gene locus from a Caucasian population and found that two of them, one in the first intron (rs967582) and one in the coding region (rs2494876), were associated with age at onset (AAO) of PD (Noureddine et al. 2005).”

What the sources say

• ?Not checked — no full text of the sourcecites Noureddine et al. 2005 source

In the paper

“The authors also found that there was augmented abundance of several mRNAs including those encoding proteins involved in neuronal development, synaptic plasticity, and neurotransmission.”

What the sources say

• ?Not checked — no full text of the sourcecites Hakak et al. 2001 source