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核 RNA 外切酶体和普遍转录:基因组功能的双重塑造者。

Nuclear RNA Exosome and Pervasive Transcription: Dual Sculptors of Genome Function.

机构信息

Division of Molecular Oncology, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.

Institute for Glyco-core Research (iGCORE), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.

出版信息

Int J Mol Sci. 2021 Dec 13;22(24):13401. doi: 10.3390/ijms222413401.

Abstract

The genome is pervasively transcribed across various species, yielding numerous non-coding RNAs. As a counterbalance for pervasive transcription, various organisms have a nuclear RNA exosome complex, whose structure is well conserved between yeast and mammalian cells. The RNA exosome not only regulates the processing of stable RNA species, such as rRNAs, tRNAs, small nucleolar RNAs, and small nuclear RNAs, but also plays a central role in RNA surveillance by degrading many unstable RNAs and misprocessed pre-mRNAs. In addition, associated cofactors of RNA exosome direct the exosome to distinct classes of RNA substrates, suggesting divergent and/or multi-layer control of RNA quality in the cell. While the RNA exosome is essential for cell viability and influences various cellular processes, mutations and alterations in the RNA exosome components are linked to the collection of rare diseases and various diseases including cancer, respectively. The present review summarizes the relationships between pervasive transcription and RNA exosome, including evolutionary crosstalk, mechanisms of RNA exosome-mediated RNA surveillance, and physiopathological effects of perturbation of RNA exosome.

摘要

基因组在各种物种中广泛转录,产生大量非编码 RNA。作为广泛转录的平衡,各种生物体都有一种核 RNA 外切体复合物,其结构在酵母和哺乳动物细胞之间是很好保守的。RNA 外切体不仅调节稳定 RNA 物种(如 rRNA、tRNA、小核仁 RNA 和小核 RNA)的加工,而且还通过降解许多不稳定的 RNA 和错误加工的前体 RNA,在 RNA 监测中发挥核心作用。此外,RNA 外切体的相关辅助因子将外切体导向不同类别的 RNA 底物,这表明细胞中 RNA 质量的控制具有不同的和/或多层次。虽然 RNA 外切体对细胞活力是必需的,并影响各种细胞过程,但 RNA 外切体成分的突变和改变分别与一系列罕见疾病和各种疾病(包括癌症)有关。本综述总结了广泛转录和 RNA 外切体之间的关系,包括进化上的串扰、RNA 外切体介导的 RNA 监测的机制,以及 RNA 外切体扰动的生理病理影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cecb/8707817/bb8f1d7e4f33/ijms-22-13401-g001.jpg

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