The RNA-binding protein SUP-12 controls muscle-specific splicing of the ADF/cofilin pre-mRNA in C. elegans.
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-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 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.
Anyanful
Akwasi
A
Department of Pathology, Emory University, Atlanta, GA 30322, USA.
Ono
Kanako
K
Johnsen
Robert C
RC
Ly
Hinh
H
Jensen
Victor
V
Baillie
David L
DL
Ono
Shoichiro
S
D051339:Actin Depolymerizing Factors; D000199:Actins / Q000378:metabolism; D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D051345:Destrin; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D024510:Muscle Development / Q000235:genetics*; D009132:Muscles / Q000166:cytology / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism*; D022821:RNA Splice Sites / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
D051339:Actin Depolymerizing Factors; D000199:Actins; D029742:Caenorhabditis elegans Proteins; D018076:DNA, Complementary; D051345:Destrin; D008840:Microfilament Proteins; D020033:Protein Isoforms; D012322:RNA Precursors; D022821:RNA Splice Sites; D016601:RNA-Binding Proteins; C495209:UNC-60 protein, C elegans