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严重急性呼吸综合征冠状病毒2型非翻译区侵入宿主RNA结合蛋白并调节细胞剪接。

The SARS-CoV-2 UTR's Intrudes Host RBP's and Modulates Cellular Splicing.

作者信息

Singh Anjali, Pandey Kush Kumar, Agrawal Shubham Kumar, Srivastava Rupesh K, Bhattacharyya Sankar, Verma Bhupendra

机构信息

Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.

Nebraska Center for Virology and School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln 68583, NE, USA.

出版信息

Adv Virol. 2023 Apr 5;2023:2995443. doi: 10.1155/2023/2995443. eCollection 2023.

Abstract

SARS-CoV-2 is a novel coronavirus that causes a potentially fatal respiratory disease known as coronavirus disease (COVID-19) and is responsible for the ongoing pandemic with increasing mortality. Understanding the host-virus interaction involved in SARS-CoV-2 pathophysiology will enhance our understanding of the mechanistic basis of COVID-19 infection. The characterization of post-transcriptional gene regulatory networks, particularly pre-mRNA splicing, and the identification and characterization of host proteins interacting with the 5' and 3'UTRs of SARS-CoV-2 will improve our understanding of post-transcriptional gene regulation during SARS-CoV-2 pathogenesis. Here, we demonstrate that either SARS-CoV-2 infection or exogenous overexpression of the 5' and 3'UTRs of the viral genomic RNAs, results in reduced mRNA levels possibly due to modulation of host cell pre-mRNA splicing. Further, we have investigated the potential RNA-binding proteins interacting with the 5' and 3'UTRs, using approaches. Our results suggest that 5' and 3'UTRs indeed interact with many RNA-binding proteins. Our results provide a primer for further investigations into the UTR-mediated regulation of splicing and related molecular mechanisms in host cells.

摘要

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)是一种新型冠状病毒,可引发一种潜在致命的呼吸道疾病,即冠状病毒病(COVID-19),并导致死亡率不断上升的持续大流行。了解SARS-CoV-2病理生理学中涉及的宿主-病毒相互作用,将增进我们对COVID-19感染机制基础的理解。转录后基因调控网络的特征,特别是前体mRNA剪接,以及与SARS-CoV-2的5'和3'非翻译区相互作用的宿主蛋白的鉴定和表征,将提高我们对SARS-CoV-2发病机制中转录后基因调控的理解。在此,我们证明,SARS-CoV-2感染或病毒基因组RNA的5'和3'非翻译区的外源性过表达,可能由于宿主细胞前体mRNA剪接的调节而导致mRNA水平降低。此外,我们使用相关方法研究了与5'和3'非翻译区相互作用的潜在RNA结合蛋白。我们的结果表明,5'和3'非翻译区确实与许多RNA结合蛋白相互作用。我们的结果为进一步研究宿主细胞中UTR介导的剪接调控及相关分子机制提供了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22cd/10098413/14770ac35e2a/AV2023-2995443.001.jpg

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