SARS-CoV-2 and HCoV-OC43 regulate host m6A modification via activation of the mTORC1 signalling pathway to facilitate viral replication.

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Tác giả: Mingzhou Chen, Xianfeng Hui, Meilin Jin, Yali Qin, Weiwei Wang, Chunbei Zhao, Shixiong Zhou

Ngôn ngữ: eng

Ký hiệu phân loại: 201 Religious mythology, general classes of religion, interreligious relations and attitudes, social theology [all formerly 291.1]

Thông tin xuất bản: United States : Emerging microbes & infections , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 629309

N6-methyladenosine (m6A) is the most prevalent post-transcriptional modification in eukaryotic RNA and is also present in various viral RNAs, where it plays a crucial role in regulating the viral life cycle. However, the molecular mechanisms through which viruses regulate host RNA m6A methylation are not fully understood. In this study, we reveal that SARS-CoV-2 and HCoV-OC43 infection enhance host m6A modification by activating the mTORC1 signalling pathway. Specifically, the viral non-structural protein nsp14 upregulates the expression of S-adenosylmethionine synthase MAT2A in an mTORC1-dependent manner. This mTORC1-MAT2A axis subsequently stimulates the synthesis of S-adenosylmethionine (SAM). The increase of SAM then enhances the m6A methylation of host RNA and facilitates viral replication. Our findings uncover a molecular mechanism by which viruses regulate host m6A methylation and provide insights into how SARS-CoV-2 hijacks host cellular epitranscriptomic modifications to promote its replication.
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