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Dcp1 的破坏导致 Aspergillus nidulans 中出现 Dcp2 依赖性异常核糖体图谱。

Disruption of Dcp1 leads to a Dcp2-dependent aberrant ribosome profiles in Aspergillus nidulans.

机构信息

Institute of Systems, Molecular and Integrative Biology, The University of Liverpool, Biosciences Building, Crown Street, Liverpool, L69 7ZB, UK.

Department of Biological Sciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, 43600 UKM, Selangor, Malaysia.

出版信息

Mol Microbiol. 2023 May;119(5):630-639. doi: 10.1111/mmi.15059. Epub 2023 Apr 6.

Abstract

There are multiple RNA degradation mechanisms in eukaryotes, key among these is mRNA decapping, which requires the Dcp1-Dcp2 complex. Decapping is involved in various processes including nonsense-mediated decay (NMD), a process by which aberrant transcripts with a premature termination codon are targeted for translational repression and rapid decay. NMD is ubiquitous throughout eukaryotes and the key factors involved are highly conserved, although many differences have evolved. We investigated the role of Aspergillus nidulans decapping factors in NMD and found that they are not required, unlike Saccharomyces cerevisiae. Intriguingly, we also observed that the disruption of one of the decapping factors, Dcp1, leads to an aberrant ribosome profile. Importantly this was not shared by mutations disrupting Dcp2, the catalytic component of the decapping complex. The aberrant profile is associated with the accumulation of a high proportion of 25S rRNA degradation intermediates. We identified the location of three rRNA cleavage sites and show that a mutation targeted to disrupt the catalytic domain of Dcp2 partially suppresses the aberrant profile of Δdcp1 strains. This suggests that in the absence of Dcp1, cleaved ribosomal components accumulate and Dcp2 may be directly involved in mediating these cleavage events. We discuss the implications of this.

摘要

真核生物中有多种 RNA 降解机制,其中关键的一种是 mRNA 去帽,这需要 Dcp1-Dcp2 复合物。去帽参与多种过程,包括无意义介导的衰变(NMD),这是一种将具有过早终止密码子的异常转录本靶向翻译抑制和快速衰变的过程。NMD 在真核生物中普遍存在,涉及的关键因素高度保守,尽管已经进化出许多差异。我们研究了 Aspergillus nidulans 去帽因子在 NMD 中的作用,发现它们不需要,与 Saccharomyces cerevisiae 不同。有趣的是,我们还观察到一种去帽因子 Dcp1 的破坏会导致核糖体谱异常。重要的是,这与破坏去帽复合物的催化成分 Dcp2 的突变不同。异常谱与高比例的 25S rRNA 降解中间产物的积累有关。我们确定了三个 rRNA 切割位点的位置,并表明靶向破坏 Dcp2 催化结构域的突变部分抑制了Δdcp1 菌株的异常谱。这表明在没有 Dcp1 的情况下,切割的核糖体成分积累,Dcp2 可能直接参与介导这些切割事件。我们讨论了这一发现的意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f00c/11497226/06f864ce1050/MMI-119-630-g006.jpg

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