RBM5 promotes exon 4 skipping of AID pre-mRNA by competing with the binding of U2AF65 to the polypyrimidine tract
RBM5 promotes exon 4 skipping of AID pre-mRNA by competing with the binding of U2AF65 to the polypyrimidine tract
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DOI：
10.1016/j.febslet.2012.09.006
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发表时间：
2012-11-02
期刊：
影响因子：
3.5
通讯作者：
Li, Xialu
中科院分区：
文献类型：
--
作者：
Jin, Wenxing;Niu, Zhaoyang;Li, Xialu
选择性剪接参与诱变酶激活诱导的胞苷脱氨酶（AID）的功能调节。然而，AID剪接调节的分子基础仍然不确定。在HeLa细胞中使用基于微型基因的筛选，我们发现RNA结合基序蛋白5（RBM 5或LUCA-15/H37）的过表达通过抑制内含子3的剪接而显著促进AID外显子4跳跃。RBM 5对内含子3剪接的抑制作用需要一个弱的3 '-剪接位点（ss）。RBM 5在体外干扰U2 AF 65与3 '-ss处多嘧啶束的结合，这表明了潜在的机制。因此，我们的研究结果不仅揭示了AID外显子4跳跃的调控机制，而且还为RBM 5在剪接调控中的功能提供了新的见解。(C)2012年欧洲生物化学学会联合会。由Elsevier B出版。V.保留所有权利。
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. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.