Translation landscape of SARS-CoV-2 noncanonical subgenomic RNAs

Kai Wu; Dehe Wang; Junhao Wang; Yu Zhou

doi:10.1016/j.virs.2022.09.003

December 2022

. doi: 10.1016/j.virs.2022.09.003

Citation: Kai Wu, Dehe Wang, Junhao Wang, Yu Zhou. Translation landscape of SARS-CoV-2 noncanonical subgenomic RNAs .VIROLOGICA SINICA, 2022, 37(6) : 813-822. http://dx.doi.org/10.1016/j.virs.2022.09.003

SARS-CoV-2非经典亚基因组RNA的翻译全景图

吴凯 ^a ,
王得和 ^a ,
王俊浩 ^a ,
周宇 ^a,b,c,d,,

a 生命科学学院,病毒学国家重点实验室,武汉大学,武汉,中国;
b 泰康生命医学中心,RNA研究所,武汉大学,武汉,中国;
c 高等研究院,武汉大学,武汉,中国;
d 免疫与代谢前沿科学中心,武汉大学,武汉,中国

通讯作者： 周宇, yu.zhou@whu.edu.cn
收稿日期： 2022-07-05
录用日期： 2022-09-01

摘要

正在发生的COVID-19大流行是由具有正链RNA基因组的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的。目前SARS-CoV-2的蛋白质组学研究主要集中于其基因组RNA（gRNA）或经典亚基因组RNA（sgRNA）所编码的蛋白质。在该论文中，我们系统地研究了SARS-CoV-2的翻译全景图，特别是非经典sgRNA的翻译。我们首先构建了一个严格的生物信息学流程vipep，通过使用RNA-seq数据和质谱数据鉴定来源于RNA病毒翻译所产生的可靠肽段。我们应用vipep分析了24组与SARS-CoV-2感染相关的质谱数据。除了已注释的蛋白外，我们鉴定到了许多来自非经典sgRNA翻译所产生的肽段，它们的表达量随感染时间稳定增加。此外，我们还探索了由非经典sgRNA编码的蛋白质的潜在功能，发现它们可以与病毒RNA结合，并可能具有免疫抗原活性。该通用型vipep流程可以适用于任何RNA病毒，这些结果扩展了SARS-CoV-2翻译图谱，为理解SARS-CoV-2 sgRNA的功能提供了新的见解。
- SARS-CoV-2
- , 亚基因组RNA（sgRNA）
- , 质谱
- , 翻译
- , RNA结合

Translation landscape of SARS-CoV-2 noncanonical subgenomic RNAs

Kai Wu ^a ,
Dehe Wang ^a ,
Junhao Wang ^a ,
Yu Zhou ^a,b,c,d,,

a State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, China;
b TaiKang Center for Life and Medical Sciences, RNA Institute, Wuhan University, Wuhan, 430072, China;
c Institute for Advanced Studies, Wuhan University, Wuhan, 430072, China;
d Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, 430072, China

Corresponding author: Yu Zhou, yu.zhou@whu.edu.cn
Received Date: 05 July 2022
Accepted Date: 01 September 2022

Abstract

The ongoing COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a positive-stranded RNA genome. Current proteomic studies of SARS-CoV-2 mainly focus on the proteins encoded by its genomic RNA (gRNA) or canonical subgenomic RNAs (sgRNAs). Here, we systematically investigated the translation landscape of SARS-CoV-2, especially its noncanonical sgRNAs. We first constructed a strict pipeline, named vipep, for identifying reliable peptides derived from RNA viruses using RNA-seq and mass spectrometry data. We applied vipep to analyze 24 sets of mass spectrometry data related to SARS-CoV-2 infection. In addition to known canonical proteins, we identified many noncanonical sgRNA-derived peptides, which stably increase after viral infection. Furthermore, we explored the potential functions of those proteins encoded by noncanonical sgRNAs and found that they can bind to viral RNAs and may have immunogenic activity. The generalized vipep pipeline is applicable to any RNA viruses and these results have expanded the SARSCoV-2 translation map, providing new insights for understanding the functions of SARS-CoV-2 sgRNAs.
- SARS-CoV-2
- , Subgenomic RNA (sgRNA)
- , Mass spectrometry
- , Translation
- , RNA binding

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