The RNA-binding protein SUP-12 controls muscle-specific splicing of the ADF/cofilin pre-mRNA in C. elegans

Akwasi Anyanful, Kanako Ono, Robert C. Johnsen, Hinh Ly, Victor Jensen, David L. Baillie, Shoichiro Ono

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Tissue-specific alternative pre-mRNA splicing is essential for increasing diversity of functionally different gene products. In Caenorhabditis elegans, UNC-60A and UNC-60B, nonmuscle and muscle isoforms of actin depolymerizing factor (ADF)/cofilin, are expressed by alternative splicing of unc-60 and regulate distinct actin-dependent developmental processes. We report that SUP-12, a member of a new family of RNA recognition motif (RRM) proteins, including SEB-4, regulates muscle-specific splicing of unc-60. In sup- 72 mutants, expression of UNC-60B is decreased, whereas UNC-60A is up-regulated in muscle, sup-72 mutations strongly suppress muscle defects in unc-60B mutants by allowing expression of UNC-60A in muscle that can substitute for UNC-60B, thus unmasking their functional redundancy. SUP-12 is expressed in muscle and localized to the nuclei in a speckled pattern. The RRM domain of SUP-12 binds to several sites of the unc-60 pre-mRNA including the UG repeats near the 3′-splice site in the first intron. Our results suggest that SUP-12 is a novel tissue-specific splicing factor and regulates functional redundancy among ADF/cofilin isoforms.

Original languageEnglish (US)
Pages (from-to)639-647
Number of pages9
JournalJournal of Cell Biology
Volume167
Issue number4
DOIs
StatePublished - Nov 22 2004

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