Interactions between mRNA export commitment, 3′-end quality control, and nuclear degradation
Interactions between mRNA export commitment, 3′-end quality control, and nuclear degradation
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DOI：
10.1128/mcb.22.23.8254-8266.2002
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发表时间：
2002-12-01
影响因子：
5.3
通讯作者：
Jensen, TH
中科院分区：
文献类型：
--
作者：
Libri, D;Dower, K;Jensen, TH
真核生物mRNA加工的几个方面与转录有关。在酿酒酵母中，mRNA输出因子Sub 2 p的过表达抑制了hpr 1无效细胞的生长缺陷，但蛋白Hpr 1 p和相关的THO蛋白复合物与转录延伸有关。事实上，我们发现热休克HSP 104转录本库在THO复合体突变体以及sub 2突变体背景中被3 '端截短。然而，令人惊讶的是，这种缺陷可以通过缺失3 '-5'核酸外切酶Rrp 6p来抑制。这表明不完整的RNA是由核降解而不是由未能有效延长转录引起的。未降解的RNA以Rrp 6p依赖性方式保留在转录位点。有趣的是，将RRP 6缺失添加到sub 2或THO复合突变体中显示出强的合成生长表型，表明未能保留和/或降解缺陷mRNA是有害的。在3 '末端加工突变体rna 14 -3和rna 15 -2中产生的mRNA，以及由自切割锤头状核酶产生的具有3'末端的RNA，也保留在Rrp 6p依赖性转录位点集中区中。两者合计，我们的研究结果表明，有缺陷的RNP的几个类别受到质量控制步骤，阻碍从转录位点焦点释放，并建议次优信使核糖核蛋白组装导致RNA降解Rrp 6p。
Several aspects of eukaryotic mRNA processing are linked to transcription. In Saccharomyces cerevisiae, overexpression of the mRNA export factor Sub2p suppresses the growth defect of hpr1 null cells,yet the protein Hpr1p and the associated THO protein complex are implicated in transcriptional elongation. Indeed, we find that a pool of heat shock HSP104 transcripts are 3'-end truncated in THO complex mutant as well as sub2 mutant backgrounds. Surprisingly, however, this defect can be suppressed by deletion of the 3'-5' exonuclease Rrp6p. This indicates that incomplete RNAs result from nuclear degradation rather than from a failure to efficiently elongate transcription. RNAs that are not degraded are retained at the transcription site in a Rrp6p-dependent manner. Interestingly, the addition of a RRP6 deletion to sub2 or to THO complex mutants shows a strong synthetic growth phenotype, suggesting that the failure to retain and/or degrade defective mRNAs is deleterious. mRNAs produced in the 3'-end processing mutants rna14-3 and rna15-2, as well as an RNA harboring a 3' end generated by a self-cleaving hammerhead ribozyme, are also retained in Rrp6p-dependent transcription site foci. Taken together, our results show that several classes of defective RNPs are subject to a quality control step that impedes release from transcription site foci and suggest that suboptimal messenger ribonucleoprotein assembly leads to RNA degradation by Rrp6p.