title: RBM5 promotes exon 4 skipping of AID pre-mRNA by competing with the binding of U2AF65 to the polypyrimidine tract.
abstract: Alternative splicing is involved in functional regulation of the mutagenic enzyme activation-induced cytidine deaminase (AID). However, the molecular basis for AID splicing regulation remains undefined. Using a mini-gene-based screen in HeLa cells, we found that overexpression of RNA binding motif protein 5 (RBM5, or LUCA-15/H37) significantly promoted AID exon 4 skipping by suppressing the splicing of intron 3. The inhibitive effect of RBM5 on intron 3 splicing required a weak 3'-splice site (ss). Indicative of the underlying mechanism, RBM5 interfered with the binding of U2AF65 to the polypyrimidine tract at the 3'-ss in vitro. Our findings thus not only shed lights on the regulatory mechanism of AID exon 4 skipping, but also provide new insights into how RBM5 functions in splicing regulation.
authors.affiliation: College of Life Sciences, Beijing Normal University, Beijing 100875, China.
authors.forename: Wenxing
authors.initials: W
authors.lastname: Jin
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Niu
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.forename: Xialu
authors.initials: X
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions; D017398:Alternative Splicing; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D003564:Cytidine Deaminase / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005091:Exons; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D012322:RNA Precursors / Q000235:genetics* / Q000378:metabolism; D022821:RNA Splice Sites; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics* / Q000378:metabolism; D000072668:Splicing Factor U2AF; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C473448:RBM5 protein, human; D012322:RNA Precursors; D022821:RNA Splice Sites; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D000072668:Splicing Factor U2AF; D025521:Tumor Suppressor Proteins; C000607494:U2AF2 protein, human; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase