Heterogeneous Nuclear Ribonucleoprotein G Regulates Splice Site Selection by Binding to CC(A/C)-rich Regions in Pre-mRNA
Heterogeneous Nuclear Ribonucleoprotein G Regulates Splice Site Selection by Binding to CC(A/C)-rich Regions in Pre-mRNA
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DOI：
10.1074/jbc.m901026200
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发表时间：
2009-05-22
影响因子：
4.8
通讯作者：
Stamm, Stefan
中科院分区：
文献类型：
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作者：
Heinrich, Bettina;Zhang, Zhaiyi;Stamm, Stefan
几乎每个编码蛋白质的基因都经历了前信使核糖核酸的剪接，并且这些前信使核糖核酸中的大部分是交替剪接的。替代外显子的使用受到蛋白质复合体在前mRNA上的瞬时形成的调节，这些蛋白质复合体通常包含异质性核糖核蛋白(HnRNPs)。在这里，我们描述了hnRNP G，一种hnRNP类蛋白质的成员。我们发现hnRNP G是一种核蛋白，在不同组织中以不同浓度表达，并与其他剪接调节蛋白相互作用。HnRNP G是超剪接小体的一部分，它以浓度依赖的方式调节选择性剪接位点的选择。它可以通过与其他剪接调控蛋白结合，在没有功能性RNA识别基序的情况下对替代外显子起作用。HnRNP G的RNA识别基序与含有CC(A/C)基序的松散共识序列结合，hnRNP G优先调节该基序聚集在附近的替代外显子。X染色体编码的hnRNP G调控不同于其Y染色体平行RNA结合基序蛋白Y连锁(RBMY)的RNA，这表明由hnRNP G和RBMY性别特异性表达引起的选择性剪接的差异可能是哺乳动物分子性别差异的原因之一。
Almost every protein-coding gene undergoes pre-mRNA splicing, and the majority of these pre-mRNAs are alternatively spliced. Alternative exon usage is regulated by the transient formation of protein complexes on the pre-mRNA that typically contain heterogeneous nuclear ribonucleoproteins (hnRNPs). Here we characterize hnRNP G, a member of the hnRNP class of proteins. We show that hnRNP G is a nuclear protein that is expressed in different concentrations in various tissues and that interacts with other splicing regulatory proteins. hnRNP G is part of the supraspliceosome, where it regulates alternative splice site selection in a concentration-dependent manner. Its action on alternative exons can occur without a functional RNA-recognition motif by binding to other splicing regulatory proteins. The RNA-recognition motif of hnRNP G binds to a loose consensus sequence containing a CC(A/C) motif, and hnRNP G preferentially regulates alternative exons where this motif is clustered in close proximity. The X-chromosomally encoded hnRNP G regulates different RNAs than its Y-chromosomal paralogue RNA-binding motif protein, Y-linked (RBMY), suggesting that differences in alternative splicing, evoked by the sex-specific expression of hnRNP G and RBMY, could contribute to molecular sex differences in mammals.