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

Abstract

T issue-specific alternative pre-mRNA splicing is essen- tial 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-12 mutants, expression of UNC-60B is decreased, whereas UNC-60A is up-regulated in muscle. sup-12 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 ex- pressed 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 regu- lates functional redundancy among ADF/cofilin isoforms.