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-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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actin Depolymerizing Factors
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Actins / metabolism
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Alternative Splicing / genetics
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Amino Acid Sequence / genetics
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Animals
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Base Sequence / genetics
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Binding Sites / genetics
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / metabolism*
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / isolation & purification
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Caenorhabditis elegans Proteins / metabolism
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Cell Nucleus / genetics
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Cell Nucleus / metabolism
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DNA, Complementary / analysis
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DNA, Complementary / genetics
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Destrin
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Microfilament Proteins / genetics
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Microfilament Proteins / metabolism*
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Molecular Sequence Data
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Muscle Development / genetics*
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Muscles / cytology
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Muscles / metabolism*
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Mutation / genetics
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Protein Structure, Tertiary / genetics
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RNA Precursors / genetics
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RNA Precursors / metabolism*
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RNA Splice Sites / genetics
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / isolation & purification
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RNA-Binding Proteins / metabolism*
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Up-Regulation / genetics
Substances
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Actin Depolymerizing Factors
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Actins
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Caenorhabditis elegans Proteins
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DNA, Complementary
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Destrin
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Microfilament Proteins
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Protein Isoforms
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RNA Precursors
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RNA Splice Sites
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RNA-Binding Proteins
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UNC-60 protein, C elegans