Cited by 78RNA Research and SplicingRNA regulation and diseaseCancer-related molecular mechanisms research

Genomic Analyses of the RNA-binding Protein Hu Antigen R (HuR) Identify a Complex Network of Target Genes and Novel Characteristics of Its Binding Sites

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Uren, Philip J., Burns, Suzanne C., Ruan, Jianhua, Singh, Kusum K., Smith, Andrew D., Penalva, Luiz O.F.·2011·Journal of Biological Chemistry

Abstract

The ubiquitously expressed RNA-binding protein Hu antigen R (HuR) or ELAVL1 is implicated in a variety of biological processes as well as being linked with a number of diseases, including cancer. Despite a great deal of prior investigation into HuR, there is still much to learn about its function. We take an important step in this direction by conducting cross-linking and immunoprecipitation and RNA sequencing experiments followed by an extensive computational analysis to determine the characteristics of the HuR binding site and impact on the transcriptome. We reveal that HuR targets predominantly uracil-rich single-stranded stretches of varying size, with a strong conservation of structure and sequence composition. Despite the fact that HuR sites are observed in intronic regions, our data do not support a role for HuR in regulating splicing. HuR sites in 3'-UTRs overlap extensively with predicted microRNA target sites, suggesting interplay between the functions of HuR and microRNAs. Network analysis showed that identified targets containing HuR binding sites in the 3' UTR are highly interconnected.

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Crossref · 10.1074/jbc.c111.266882

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  • Hu binding sites are mostly located in 3′ UTRs of mRNAs, with a significant portion in introns and relatively few in 5′ UTRs.

    “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.”

    From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Uren et al. 2011

    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)

    Experimental — accuracy not yet measured
  • High-throughput analyses of HuR and nELAV target mRNAs demonstrate that all four Hu proteins preferentially bind U-rich sequences interspersed with Gs or As.

    “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;”

    From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Uren et al. 2011

    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)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 5

  1. [5]5. Mittal, N., Roy, N., Babu, M. M., and Janga, S. C. (2009) Proc. Natl. Acad. Sci. U.S.A. 106, 20300-20305
  2. [8]8. Srikantan, S., and M. Gorospe (2011) Front. Biomed. Sci. , in press
  3. [13]13. López de Silanes, I., Zhan, M., Lal, A., Yang, X., and Gorospe, M. (2004) Proc. Natl. Acad. Sci. U.S.A. 101, 2987-2992
  4. [26]26. Smith, A. D., Sumazin, P., and Zhang, M. Q. (2005) Proc. Natl. Acad. Sci. U.S.A. 102, 1560-1565
  5. [27]27. Smith, A. D., Sumazin, P., Xuan, Z., and Zhang, M. Q. (2006) Proc. Natl. Acad. Sci. U.S.A. 103, 6275-6280

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Authors
Uren, P. J., Burns, S. C., Ruan, J., Singh, K. K., Smith, A. D., & Penalva, L. O. F.
Affiliations
  • University of Southern California (US)
  • The University of Texas at San Antonio Health Science Center (US)
  • The University of Texas at San Antonio (US)
Corresponding author
  • Smith, Andrew D.
  • Penalva, Luiz O.F.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2011-10
Volume
286
Issue
43
Pages
37063-37066
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2086534524
Cited by
78
References
39
Citations by year
2025: 3 · 2024: 5 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 1 · 2018: 6 · 2017: 5 · 2016: 2 · 2015: 14 · 2014: 12 · 2013: 7 · 2012: 10
FWCI
3.90
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r21hg004664-02)
  • National Human Genome Research Institute (5R21HG004664-02, R21 HG004664)
  • National Institute of General Medical Sciences (SC3GM086305)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords
HuR, RNA-binding proteins, 3' untranslated region, microRNA binding sites, RNA splicing, transcriptome, gene regulatory networks
MeSH terms
HeLa Cells, Humans, Response Elements, 3' Untranslated Regions, Genomics, MicroRNAs, ELAV Proteins

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