Journal Article

All three RNA recognition motifs and the hinge region of HuC play distinct roles in the regulation of alternative splicing

Melissa N. Hinman, Hua-Lin Zhou, Alok Sharma and Hua Lou

in Nucleic Acids Research

Volume 41, issue 9, pages 5049-5061
Published in print May 2013 | ISSN: 0305-1048
Published online March 2013 | e-ISSN: 1362-4962 | DOI: http://dx.doi.org/10.1093/nar/gkt166

More Like This

Show all results sharing these subjects:

  • Chemistry
  • Biochemistry
  • Bioinformatics and Computational Biology
  • Genetics and Genomics
  • Molecular and Cell Biology

GO

Show Summary Details

Preview

The four Hu [embryonic lethal abnormal vision-like (ELAVL)] protein family members regulate alternative splicing by binding to U-rich sequences surrounding target exons and affecting the interaction of the splicing machinery and/or local chromatin modifications. Each of the Hu proteins contains a divergent N-terminus, three highly conserved RNA recognition motifs (RRM1, RRM2 and RRM3) and a hinge region separating RRM2 and RRM3. The roles of each domain in splicing regulation are not well understood. Here, we investigate how HuC, a relatively poorly characterized family member, regulates three target pre-mRNAs: neurofibromatosis type I, Fas and HuD. We find that the HuC N-terminus is dispensable for splicing regulation, and the three RRMs are required for splicing regulation of each target, whereas the hinge region contributes to regulation of only some targets. Interestingly, the regions of the hinge and RRM3 required for regulating different targets only partially overlap, implying substrate-specific mechanisms of HuC-mediated splicing regulation. We show that RRM1 and RRM2 are required for binding to target pre-mRNAs, whereas the hinge and RRM3 are required for HuC–HuC self-interaction. Finally, we find that the portions of RRM3 required for HuC–HuC interaction overlap with those required for splicing regulation of all three targets, suggesting a role of HuC–HuC interaction in splicing regulation.

Journal Article.  8209 words.  Illustrated.

Subjects: Chemistry ; Biochemistry ; Bioinformatics and Computational Biology ; Genetics and Genomics ; Molecular and Cell Biology

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.