The 3′ to 5′ degradation of yeast mRNAs is a general mechanism for mRNA turnover that requires the SKI2 DEVH box protein and 3′ to 5′ exonucleases of the exosome complex

The 3′ to 5′ degradation of yeast mRNAs is a general mechanism for mRNA turnover that requires the SKI2 DEVH box protein and 3′ to 5′ exonucleases of the exosome complex
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DOI:
10.1093/emboj/17.5.1497
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发表时间:
1998-03-02
期刊:
影响因子:
11.4
通讯作者:
Parker, R
Parker, R
中科院分区:
生物学1区
文献类型:
--
作者:
Anderson, JSJ;Parker, R

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在酵母中,mRNA衰变的一个主要途径是通过去烷基化依赖性脱帽发生,这将转录物暴露于5‘至3’外核溶解降解中。我们发现,酵母中mRNA衰变的第二种一般途径是转录物的3‘至5’降解。我们还发现,mRNA的3‘至5’降解需要SK12、SK13、SK16/RRP41、SK18和RRP4基因产物。Ski6p/Rrp41p蛋白与大肠杆菌3‘至5’外核糖核酸酶RNase PH具有同源性,并且Ski6p/Rrp41p和Rrp4p蛋白都是称为外显体的多蛋白复合物的组成部分。含有至少三个具有3′至5′外核糖核酸酶活性的多肽。这些观察结果表明,外泌体可能是在3′~ 5′方向上降解mRNA体的溶核活性,并且外泌体对mRNA的活性可能受到Ski2p、Ski3p和Ski8p的调节,阻断3′~ 5′和5′~ 3′衰变导致无法生存,条件双突变体表现出极长的mRNA半衰期。这些观察结果表明,有效的mRNA周转是生存能力所必需的,我们已经确定了酵母中mRNA衰变的两种主要途径。
One major pathway of mRNA decay in yeast occurs by deadenylation-dependent decapping, which exposes the transcript to 5' to 3' exonucleolytic degradation. We show that a second general pathway of mRNA decay in yeast occurs by 3' to 5' degradation of the transcript, We also show that the SK12, SK13, SK16/RRP41, SK18 and RRP4 gene products are required for 3' to 5' decay of mRNA, The Ski6p/Rrp41p protein has homology to the Escherichia coli 3' to 5' exoribonuclease RNase PH, and both the Ski6p/Rrp41p and Rrp4p proteins are components of a multiprotein complex, termed the exosome, that contains at least three polypeptides with 3' to 5' exoribonuclease activities. These observations suggest that the exosome may be the nucleolytic activity that degrades the body of the mRNA in a 3' to 5' direction, and the exosome's activity on mRNAs may be modulated by Ski2p, Ski3p and Ski8p, Blocking both 3' to 5' and 5' to 3' decay leads to inviability, and conditional double mutants show extremely long mRNA half-lives. These observations argue that efficient mRNA turnover is required for viability and that we have identified the two major pathways of mRNA decay in yeast.