Details

Autor(en) / Beteiligte

• Gokhale, Nandan S.
• McIntyre, Alexa B.R.
• McFadden, Michael J.
• Roder, Allison E.
• Kennedy, Edward M.
• Gandara, Jorge A.
• Hopcraft, Sharon E.
• Quicke, Kendra M.
• Vazquez, Christine
• Willer, Jason
• Ilkayeva, Olga R.
• Law, Brittany A.
• Holley, Christopher L.
• Garcia-Blanco, Mariano A.
• Evans, Matthew J.
• Suthar, Mehul S.
• Bradrick, Shelton S.
• Mason, Christopher E.
• Horner, Stacy M.

Titel

N6-Methyladenosine in Flaviviridae Viral RNA Genomes Regulates Infection

Ist Teil von

• Cell host & microbe, 2016-11, Vol.20 (5), p.654-665

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The RNA modification N6-methyladenosine (m6A) post-transcriptionally regulates RNA function. The cellular machinery that controls m6A includes methyltransferases and demethylases that add or remove this modification, as well as m6A-binding YTHDF proteins that promote the translation or degradation of m6A-modified mRNA. We demonstrate that m6A modulates infection by hepatitis C virus (HCV). Depletion of m6A methyltransferases or an m6A demethylase, respectively, increases or decreases infectious HCV particle production. During HCV infection, YTHDF proteins relocalize to lipid droplets, sites of viral assembly, and their depletion increases infectious viral particles. We further mapped m6A sites across the HCV genome and determined that inactivating m6A in one viral genomic region increases viral titer without affecting RNA replication. Additional mapping of m6A on the RNA genomes of other Flaviviridae, including dengue, Zika, yellow fever, and West Nile virus, identifies conserved regions modified by m6A. Altogether, this work identifies m6A as a conserved regulatory mark across Flaviviridae genomes. [Display omitted] •The RNA genomes of HCV, ZIKV, DENV, YFV, and WNV contain m6A modification•The cellular m6A machinery regulates HCV infectious particle production•YTHDF proteins reduce HCV particle production and localize at viral assembly sites•m6A-abrogating mutations in HCV E1 increase infectious particle production N6-methyladenosine (m6A) post-transcriptionally regulates RNA function. Gokhale et al. demonstrate that the RNA genomes of HCV, ZIKV, DENV, YFV, and WNV are modified by m6A. Depletion of cellular machinery that regulates m6A or introduction of m6A-abrogating mutations within HCV RNA increase viral particle production, suggesting that m6A negatively regulates HCV.