U2 snRNP is required for expression of the 3' end of genes.
U2 snRNP is required for expression of the 3' end of genes.
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DOI：
10.1371/journal.pone.0098015
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kaida D
中科院分区：
文献类型：
--
作者：
Koga M;Satoh T;Takasaki I;Kawamura Y;Yoshida M;Kaida D
真核生物中的前mRNA会进行mRNA加工，包括加帽、聚腺苷酸化和剪接。转录和mRNA加工是耦合的，这种耦合刺激mRNA加工;然而，mRNA加工对转录的影响尚未完全了解。在这项研究中，我们发现剪接抑制剂spliceostatin A（SSA）或U2 snRNA的反义寡核苷酸抑制U2 snRNP，导致基因特异性3′端下调。从培养基中去除SSA恢复了基因3′端的表达，表明U2 snRNP是基因3′端表达所必需的。最后，我们发现SSA处理导致Pol II在3′端下调基因如CDK 6、SMEK 2和EGFR的5′端附近聚集，表明SSA处理导致这些基因的转录延长停滞。这些发现表明，U2 snRNP可能通过调节转录延伸对全长mRNA的产生很重要，并且新的检查点机制防止前mRNA由于剪接缺陷而积累，从而防止可能通过阻止转录延伸从前mRNA翻译的异常蛋白质的产生。
Pre-mRNA in eukaryotes is subjected to mRNA processing, which includes capping, polyadenylation, and splicing. Transcription and mRNA processing are coupled, and this coupling stimulates mRNA processing; however, the effects of mRNA processing on transcription are not fully understood. In this study, we found that inhibition of U2 snRNP by a splicing inhibitor, spliceostatin A (SSA), or by an antisense oligonucleotide to U2 snRNA, caused gene-specific 3′-end down-regulation. Removal of SSA from the culture media restored expression of the 3′ ends of genes, suggesting that U2 snRNP is required for expression of the 3′ end of genes. Finally, we found that SSA treatment caused accumulation of Pol II near the 5′ end of 3′-end down regulated genes, such as CDK6, SMEK2 and EGFR, indicating that SSA treatment led to transcription elongation arrest on these genes. These findings suggest that U2 snRNP is important for production of full length mRNA probably through regulation of transcription elongation, and that a novel checkpoint mechanism prevents pre-mRNA from accumulating as a result of splicing deficiencies, and thereby prevents production of aberrant proteins that might be translated from pre-mRNAs through the arrest of transcription elongation.
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