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Cited by 113RNA Research and SplicingGenetics and Neurodevelopmental DisordersRNA regulation and disease

Novel recognition motifs and biological functions of the RNA-binding protein HuD revealed by genome-wide identification of its targets

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Bolognani, Federico, Contente-Cuomo, Tania, Perrone-Bizzozero, Nora I.·2010·Nucleic Acids Research
DOI 10.1093/nar/gkp863PMC PMC2800223
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Abstract

HuD is a neuronal ELAV-like RNA-binding protein (RBP) involved in nervous system development, regeneration, and learning and memory. This protein stabilizes mRNAs by binding to AU-rich instability elements (AREs) in their 3' unstranslated regions (3' UTR). To isolate its in vivo targets, messenger ribonucleoprotein (mRNP) complexes containing HuD were first immunoprecipitated from brain extracts and directly bound mRNAs identified by subsequent GST-HuD pull downs and microarray assays. Using the 3' UTR sequences of the most enriched targets and the known sequence restrictions of the HuD ARE-binding site, we discovered three novel recognition motifs. Motifs 2 and 3 are U-rich whereas motif 1 is C-rich. In vitro binding assays indicated that HuD binds motif 3 with the highest affinity, followed by motifs 2 and 1, with less affinity. These motifs were found to be over-represented in brain mRNAs that are upregulated in HuD overexpressor mice, supporting the biological function of these sequences. Gene ontology analyses revealed that HuD targets are enriched in signaling pathways involved in neuronal differentiation and that many of these mRNAs encode other RBPs, translation factors and actin-binding proteins. These findings provide further insights into the post-transcriptional mechanisms by which HuD promotes neural development and synaptic plasticity.

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Authors
Bolognani, F., Contente-Cuomo, T., & Perrone-Bizzozero, N. I.
Affiliations
University of New Mexico (US)
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2009-10-21
Volume
38
Issue
1
Pages
117-130
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkp863
PMC
PMC2800223
OpenAlex
W2125262718
Cited by
113
References
4
Citations by year
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FWCI
3.36
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (NS 30255, R01NS030255)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords
HUD, AU-rich elements, mRNA stabilization, 3' untranslated region, recognition motifs, messenger ribonucleoprotein complexes, neuronal differentiation, synaptic plasticity, neural development, post-transcriptional regulation, brain gene expression
MeSH terms
Animals, Binding Sites, Brain, Mice, Transgenic, RNA, Messenger, Up-Regulation, Genome, Sequence Analysis, RNA, 3' Untranslated Regions, Mice, ELAV Proteins

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