CUGBP1 and MBNL1 preferentially bind to 3' UTRs and facilitate mRNA decay.
CUGBP1 and MBNL1 preferentially bind to 3' UTRs and facilitate mRNA decay.
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DOI：
10.1038/srep00209
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发表时间：
2012
影响因子：
4.6
通讯作者：
Ohno K
中科院分区：
文献类型：
--
作者：
Masuda A;Andersen HS;Doktor TK;Okamoto T;Ito M;Andresen BS;Ohno K
CUGBP 1和MBNL 1是发育调节的RNA结合蛋白，与强直性肌营养不良1型有因果关系。我们全面确定了CUGBP 1和MBNL 1的体内RNA结合位点。有趣的是，CUGBP 1和MBNL 1都优先与3′ UTR结合。CUGBP 1和MBNL 1结合的3′ UTR的分析表明，这两种因子介导加速mRNA衰变，表达阵列的时间分布支持这一点。CUGBP 1在加速mRNA衰变中的作用先前已有报道，但迄今为止尚未报道MBNL 1的类似功能。已经确定CUGBP 1和MBNL 1调节可变剪接。通过外显子阵列筛选和RT-PCR验证显示CUGBP 1和MBNL 1结合位点对所产生的选择性剪接模式的位置依赖性。这项研究表明，CUGBP 1和MBNL 1的调节对于准确控制广谱mRNA的不稳定以及选择性剪接事件至关重要。
CUGBP1 and MBNL1 are developmentally regulated RNA-binding proteins that are causally associated with myotonic dystrophy type 1. We globally determined the in vivo RNA-binding sites of CUGBP1 and MBNL1. Interestingly, CUGBP1 and MBNL1 are both preferentially bound to 3′ UTRs. Analysis of CUGBP1- and MBNL1-bound 3′ UTRs demonstrated that both factors mediate accelerated mRNA decay and temporal profiles of expression arrays supported this. Role of CUGBP1 on accelerated mRNA decay has been previously reported, but the similar function of MBNL1 has not been reported to date. It is well established that CUGBP1 and MBNL1 regulate alternative splicing. Screening by exon array and validation by RT-PCR revealed position dependence of CUGBP1- and MBNL1-binding sites on the resulting alternative splicing pattern. This study suggests that regulation of CUGBP1 and MBNL1 is essential for accurate control of destabilization of a broad spectrum of mRNAs as well as of alternative splicing events.