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Nrd1p identifies aberrant and natural exosomal target messages during the nuclear mRNA surveillance in Saccharomyces cerevisiae
bioRxiv - Molecular Biology Pub Date : 2020-10-16 , DOI: 10.1101/2020.06.02.129106
Pragyan Singh , Anusha Chaudhuri , Mayukh Banerjea , Neeraja Marathe , Biswadip Das

In all eukaryotes, selective nuclear degradation of aberrant mRNAs by nuclear exosome and its cofactors TRAMP, and CTEXT contribute to the fidelity of the gene expression pipeline. In the model eukaryote, Saccharomyces cerevisiae, the Nrd1p-Nab3p-Sen1p (NNS) complex, previously known to be involved in the transcription termination and matured 3'-end formation of vast majority of non-coding and several coding RNAs, is demonstrated to universally participate in the nuclear decay of various kinds of faulty messages in this study. Consistently, nrd1-1/nrd1-2 mutant cells display impairment of the decay of all kinds of aberrant mRNAs, like the yeast mutants deficient in Rrp41p, Rrp6p, and Rrp4p. nrd1deltaCID mutation (consisting of Nrd1p lacking its CID domain thereby abrogating its interaction with RNAPII) however, abolishes the decay of aberrant messages generated during early phases of mRNP biogenesis (transcription elongation, splicing and 3'-end maturation) without affecting the decay rate of the export-defective mRNAs. Mutation in the 3'-end processing factor, Pcf11p, in contrast, displayed a selective abolition of the decay of the aberrant mRNAs, generated at the late phase of mRNP biogenesis (export-defective mRNAs) without influencing the faulty messages spawned in the early phase of mRNP biogenesis. Co-transcriptional recruitment of Nrd1p onto the faulty messages, which relies on RNAPII during transcription elongation and on Pcf11p post transcription, is vital for the exosomal decay of aberrant mRNAs, as Nrd1p deposition on the export-defective messages led to the Rrp6p recruitment and eventually, their decay. Thus, presence of the Nrd1p mark on aberrant mRNAs appears rate-limiting for the distinction of the aberrant messages from their normal functional counterparts.

中文翻译:

Nrd1p在酿酒酵母的核mRNA监测过程中识别异常和天然的外泌体靶标信息

在所有真核生物中,核外泌体及其辅助因子TRAMP和CTEXT对异常mRNA的选择性核降解有助于基因表达管线的保真度。在真核生物模型酿酒酵母中,Nrd1p-Nab3p-Sen1p(NNS)复合物以前已知参与转录终止和绝大多数非编码RNA和几种编码RNA的3'端形成,因此能够在这项研究中普遍参与了各种故障信息的核衰变。一致地,nrd1-1 / nrd1-2突变细胞表现出对各种异常mRNA的衰变的损害,例如缺乏Rrp41p,Rrp6p和Rrp4p的酵母突变体。nrd1deltaCID突变(由缺少其CID域的Nrd1p组成,从而废除了它与RNAPII的相互作用),消除了在mRNP生物发生的早期阶段(转录延伸,剪接和3'-末端成熟)产生的异常信息的衰减,而不会影响输出缺陷mRNA的衰减率。相反,在3'末端加工因子Pcf11p中的突变显示出选择性消除了mRNP生物发生后期(出口缺陷型mRNA)产生的异常mRNA的衰变,而不会影响早期产生的错误信息。阶段的mRNP生物发生。将Nrd1p共转录募集到有缺陷的信息上,这依赖于转录延长过程中的RNAPII和转录后的Pcf11p,对于异常mRNA的外体衰变至关重要,因为Nrd1p在出口缺陷信息上的沉积导致Rrp6p募集并最终,它们的衰变。从而,
更新日期:2020-10-17
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