論文 - 詳細
| RRC ID | 81714 |
|---|---|
| 著者 | Katahira J, Ohmae T, Yasugi M, Sasaki R, Itoh Y, Kohda T, Hieda M, Yokota Hirai M, Okamoto T, Miyamoto Y. |
| タイトル | Nsp14 of SARS-CoV-2 inhibits mRNA processing and nuclear export by targeting the nuclear cap-binding complex. |
| ジャーナル | Nucleic Acids Res |
| Abstract |
To facilitate selfish replication, viruses halt host gene expression in various ways. The nuclear export of mRNA is one such process targeted by many viruses. SARS-CoV-2, the etiological agent of severe acute respiratory syndrome, also prevents mRNA nuclear export. In this study, Nsp14, a bifunctional viral replicase subunit, was identified as a novel inhibitor of mRNA nuclear export. Nsp14 induces poly(A)+ RNA nuclear accumulation and the dissolution/coalescence of nuclear speckles. Genome-wide gene expression analysis revealed the global dysregulation of splicing and 3'-end processing defects of replication-dependent histone mRNAs by Nsp14. These abnormalities were also observed in SARS-CoV-2-infected cells. A mutation introduced at the guanine-N7-methyltransferase active site of Nsp14 diminished these inhibitory activities. Targeted capillary electrophoresis-mass spectrometry analysis (CE-MS) unveiled the production of N7-methyl-GTP in Nsp14-expressing cells. Association of the nuclear cap-binding complex (NCBC) with the mRNA cap and subsequent recruitment of U1 snRNP and the stem-loop binding protein (SLBP) were impaired by Nsp14. These data suggest that the defects in mRNA processing and export arise from the compromise of NCBC function by N7-methyl-GTP, thus exemplifying a novel viral strategy to block host gene expression. |
| 巻・号 | 51(14) |
| ページ | 7602-7618 |
| 公開日 | 2023-8-11 |
| DOI | 10.1093/nar/gkad483 |
| PII | 7187708 |
| PMID | 37260089 |
| PMC | PMC10415132 |
| MeSH | Active Transport, Cell Nucleus* COVID-19* / virology Exoribonucleases / metabolism Guanosine Triphosphate / metabolism Humans RNA, Messenger* / metabolism RNA, Viral / genetics RNA, Viral / metabolism SARS-CoV-2* / metabolism Viral Nonstructural Proteins* / metabolism |
| IF | 11.502 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 39 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pENTR4-GFP-Nsp14-BGHpA (RDB20274) pCMV-FLAG3-DcpS (RDB20275) pENTR4-GFP-DcpS-BGHpA (RDB20276) |