Anyanful Akwasi, Ono Kanako, Johnsen Robert C, Ly Hinh, Jensen Victor, Baillie David L, Ono Shoichiro
Department of Pathology, Emory University, Atlanta, GA 30322, USA.
J Cell Biol. 2004 Nov 22;167(4):639-47. doi: 10.1083/jcb.200407085. Epub 2004 Nov 15.
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.
组织特异性的前体mRNA可变剪接对于增加功能不同的基因产物的多样性至关重要。在秀丽隐杆线虫中，肌动蛋白解聚因子（ADF）/切丝蛋白的非肌肉和肌肉异构体UNC-60A和UNC-60B，通过unc-60的可变剪接表达，并调节不同的肌动蛋白依赖性发育过程。我们报道，SUP-12是一个新的RNA识别基序（RRM）蛋白家族的成员，包括SEB-4，它调节unc-60的肌肉特异性剪接。在sup-12突变体中，UNC-60B的表达降低，而UNC-60A在肌肉中上调。sup-12突变通过允许UNC-60A在肌肉中表达来强烈抑制unc-60B突变体中的肌肉缺陷，UNC-60A可以替代UNC-60B，从而揭示它们的功能冗余。SUP-12在肌肉中表达，并以斑点状模式定位于细胞核。SUP-12的RRM结构域与unc-60前体mRNA的几个位点结合，包括第一个内含子中3'-剪接位点附近的UG重复序列。我们的结果表明，SUP-12是一种新型的组织特异性剪接因子，并调节ADF/切丝蛋白异构体之间的功能冗余。
