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Rat1在将mRNA 3'末端加工与转录终止相偶联中的作用:对统一变构-鱼雷模型的启示

The role of Rat1 in coupling mRNA 3'-end processing to transcription termination: implications for a unified allosteric-torpedo model.

作者信息

Luo Weifei, Johnson Arlen W, Bentley David L

机构信息

Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, University of Colorado Health Sciences Center at Fitzsimons, Aurora, Colorado 80045, USA.

出版信息

Genes Dev. 2006 Apr 15;20(8):954-65. doi: 10.1101/gad.1409106. Epub 2006 Apr 5.

DOI:10.1101/gad.1409106
PMID:16598041
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1472303/
Abstract

The torpedo model of transcription termination by RNA polymerase II proposes that a 5'-3' RNA exonuclease enters at the poly(A) cleavage site, degrades the nascent RNA, and eventually displaces polymerase from the DNA. Cotranscriptional degradation of nascent RNA has not been directly demonstrated, however. Here we report that two exonucleases, Rat1 and Xrn1, both contribute to cotranscriptional degradation of nascent RNA, but this degradation is not sufficient to cause polymerase release. Unexpectedly, Rat1 functions in both 3'-end processing and termination by enhancing recruitment of 3'-end processing factors, including Pcf11 and Rna15. In addition, the cleavage factor Pcf11 reciprocally aids in recruitment of Rat1 to the elongation complex. Our results suggest a unified allosteric/torpedo model in which Rat1 is not a dedicated termination factor, but is an integrated component of the cleavage/polyadenylation apparatus.

摘要

RNA聚合酶II转录终止的鱼雷模型提出,一种5'-3' RNA核酸外切酶在聚腺苷酸化切割位点进入,降解新生RNA,并最终将聚合酶从DNA上置换下来。然而,新生RNA的共转录降解尚未得到直接证实。在此我们报告,两种核酸外切酶Rat1和Xrn1都参与新生RNA的共转录降解,但这种降解不足以导致聚合酶释放。出乎意料的是,Rat1通过增强包括Pcf11和Rna15在内的3'端加工因子的募集,在3'端加工和终止过程中都发挥作用。此外,切割因子Pcf11反过来有助于将Rat1募集到延伸复合物中。我们的结果提出了一个统一的变构/鱼雷模型,其中Rat1不是一个专门的终止因子,而是切割/聚腺苷酸化装置的一个整合组分。

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本文引用的文献

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The polyadenylation factor CPSF-73 is involved in histone-pre-mRNA processing.聚腺苷酸化因子CPSF-73参与组蛋白前体mRNA的加工过程。
Cell. 2005 Oct 7;123(1):37-48. doi: 10.1016/j.cell.2005.08.002.
2
Rat1p and Rai1p function with the nuclear exosome in the processing and degradation of rRNA precursors.Rat1p和Rai1p在核糖体RNA前体的加工和降解过程中与核外切体共同发挥作用。
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CTD-dependent dismantling of the RNA polymerase II elongation complex by the pre-mRNA 3'-end processing factor, Pcf11.由前体mRNA 3'末端加工因子Pcf11介导的依赖CTD的RNA聚合酶II延伸复合物的拆解
Genes Dev. 2005 Jul 1;19(13):1572-80. doi: 10.1101/gad.1296305.
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Altered nucleosome occupancy and histone H3K4 methylation in response to 'transcriptional stress'.响应“转录应激”时核小体占据率及组蛋白H3K4甲基化的改变
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Connections between mRNA 3' end processing and transcription termination.信使核糖核酸3'端加工与转录终止之间的联系。
Curr Opin Cell Biol. 2005 Jun;17(3):257-61. doi: 10.1016/j.ceb.2005.04.003.
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The transcriptional coactivator PC4/Sub1 has multiple functions in RNA polymerase II transcription.转录共激活因子PC4/Sub1在RNA聚合酶II转录过程中具有多种功能。
EMBO J. 2005 Mar 9;24(5):1009-20. doi: 10.1038/sj.emboj.7600575. Epub 2005 Feb 3.
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