دورية أكاديمية
The methyltransferase domain of the Respiratory Syncytial Virus L protein catalyzes cap N7 and 2'-O-methylation.
| العنوان: | The methyltransferase domain of the Respiratory Syncytial Virus L protein catalyzes cap N7 and 2'-O-methylation. |
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| المؤلفون: | Priscila Sutto-Ortiz, Sergey Tcherniuk, Nina Ysebaert, Pravien Abeywickrema, Mathieu Noël, Alice Decombe, Françoise Debart, Jean-Jacques Vasseur, Bruno Canard, Dirk Roymans, Peter Rigaux, Jean-François Eléouët, Etienne Decroly |
| المصدر: | PLoS Pathogens, Vol 17, Iss 5, p e1009562 (2021) |
| بيانات النشر: | Public Library of Science (PLoS), 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Immunologic diseases. Allergy LCC:Biology (General) |
| مصطلحات موضوعية: | Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5 |
| الوصف: | Respiratory syncytial virus (RSV) is a negative sense single-stranded RNA virus and one of the main causes of severe lower respiratory tract infections in infants and young children. RSV RNA replication/transcription and capping are ensured by the viral Large (L) protein. The L protein contains a polymerase domain associated with a polyribonucleotidyl transferase domain in its N-terminus, and a methyltransferase (MTase) domain followed by the C-terminal domain (CTD) enriched in basic amino acids at its C-terminus. The MTase-CTD of Mononegavirales forms a clamp to accommodate RNA that is subsequently methylated on the cap structure and depending on the virus, on internal positions. These enzymatic activities are essential for efficient viral mRNA translation into proteins, and to prevent the recognition of uncapped viral RNA by innate immunity sensors. In this work, we demonstrated that the MTase-CTD of RSV, as well as the full-length L protein in complex with phosphoprotein (P), catalyzes the N7- and 2'-O-methylation of the cap structure of a short RNA sequence that corresponds to the 5' end of viral mRNA. Using different experimental systems, we showed that the RSV MTase-CTD methylates the cap structure with a preference for N7-methylation as first reaction. However, we did not observe cap-independent internal methylation, as recently evidenced for the Ebola virus MTase. We also found that at μM concentrations, sinefungin, a S-adenosylmethionine analogue, inhibits the MTase activity of the RSV L protein and of the MTase-CTD domain. Altogether, these results suggest that the RSV MTase domain specifically recognizes viral RNA decorated by a cap structure and catalyzes its methylation, which is required for translation and innate immune system subversion. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1553-7366 1553-7374 |
| Relation: | https://doaj.org/toc/1553-7366; https://doaj.org/toc/1553-7374 |
| DOI: | 10.1371/journal.ppat.1009562 |
| URL الوصول: | https://doaj.org/article/70047fcf48b749b8834adc4f16a949f7 |
| رقم الأكسشن: | edsdoj.70047fcf48b749b8834adc4f16a949f7 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15537366 15537374 |
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| DOI: | 10.1371/journal.ppat.1009562 |