The RNA binding protein RNPS1 alleviates ASF/SF2 depletion-induced genomic instability
The RNA binding protein RNPS1 alleviates ASF/SF2 depletion-induced genomic instability
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DOI：
10.1261/rna.734407
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发表时间：
2007-12-01
期刊：
影响因子：
4.5
通讯作者：
Manley, James L.
中科院分区：
文献类型：
--
作者：
Li, Xialu;Niu, Tianhui;Manley, James L.
转录诱导的R环的形成对整个进化过程中的基因组完整性构成了严重威胁。我们最近发现，SR蛋白ASF/SF 2通过与新生mRNA前体共转录结合以防止其与模板DNA再结合来防止脊椎动物中的R环形成。在这里，我们确定了另一种RNA结合蛋白，RNPS 1，当过表达强烈抑制高分子量（HMW）DNA片段，超突变，G2细胞周期停滞表型的ASF/SF 2耗尽的细胞。此外，在HeLa细胞中通过RNA干扰去除RNPS 1导致HMW DNA片段的积累。由于ASF/SF 2缺失不影响RNPS 1的表达，并且RNPS 1不能补偿ASF/SF 2在剪接中的功能，我们的数据表明RNPS 1能够与ASF/SF 2一起在新生转录物上形成RNP复合物，从而防止转录R环的形成。
Formation of transcription-induced R-loops poses a critical threat to genomic integrity throughout evolution. We have recently shown that the SR protein ASF/SF2 prevents R-loop formation in vertebrates by cotranscriptionally binding to nascent mRNA precursors to prevent their reassociation with template DNA. Here, we identify another RNA binding protein, RNPS1, that when overexpressed strongly suppresses the high molecular weight (HMW) DNA fragmentation, hypermutation, and G2 cell cycle arrest phenotypes of ASF/SF2-depleted cells. Furthermore, ablation of RNPS1 by RNA interference in HeLa cells leads to accumulation of HMW DNA fragments. As ASF/SF2 depletion does not influence RNPS1 expression, and RNPS1 cannot compensate for ASF/SF2 function in splicing, our data suggest that RNPS1 is able to function together with ASF/SF2 to form RNP complexes on nascent transcripts, and thereby prevent formation of transcriptional R-loops.