Your browser doesn't support javascript.
loading
Targeting the m6A RNA modification pathway blocks SARS-CoV-2 and HCoV-OC43 replication.
Burgess, Hannah M; Depledge, Daniel P; Thompson, Letitia; Srinivas, Kalanghad Puthankalam; Grande, Rebecca C; Vink, Elizabeth I; Abebe, Jonathan S; Blackaby, Wesley P; Hendrick, Alan; Albertella, Mark R; Kouzarides, Tony; Stapleford, Kenneth A; Wilson, Angus C; Mohr, Ian.
Afiliación
  • Burgess HM; Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA.
  • Depledge DP; Department of Medicine, New York University School of Medicine, New York, New York 10016, USA.
  • Thompson L; Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA.
  • Srinivas KP; Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA.
  • Grande RC; Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA.
  • Vink EI; Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA.
  • Abebe JS; Department of Medicine, New York University School of Medicine, New York, New York 10016, USA.
  • Blackaby WP; Storm Therapeutics Ltd, Cambridge CB22 3AT, United Kingdom.
  • Hendrick A; Storm Therapeutics Ltd, Cambridge CB22 3AT, United Kingdom.
  • Albertella MR; Storm Therapeutics Ltd, Cambridge CB22 3AT, United Kingdom.
  • Kouzarides T; The Gurdon Institute, Department of Pathology, University of Cambridge, Cambridge CB2 1QN, United Kingdom.
  • Stapleford KA; Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA.
  • Wilson AC; Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA.
  • Mohr I; Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA.
Genes Dev ; 35(13-14): 1005-1019, 2021 07 01.
Article en En | MEDLINE | ID: mdl-34168039
N6-methyladenosine (m6A) is an abundant internal RNA modification, influencing transcript fate and function in uninfected and virus-infected cells. Installation of m6A by the nuclear RNA methyltransferase METTL3 occurs cotranscriptionally; however, the genomes of some cytoplasmic RNA viruses are also m6A-modified. How the cellular m6A modification machinery impacts coronavirus replication, which occurs exclusively in the cytoplasm, is unknown. Here we show that replication of SARS-CoV-2, the agent responsible for the COVID-19 pandemic, and a seasonal human ß-coronavirus HCoV-OC43, can be suppressed by depletion of METTL3 or cytoplasmic m6A reader proteins YTHDF1 and YTHDF3 and by a highly specific small molecule METTL3 inhibitor. Reduction of infectious titer correlates with decreased synthesis of viral RNAs and the essential nucleocapsid (N) protein. Sites of m6A modification on genomic and subgenomic RNAs of both viruses were mapped by methylated RNA immunoprecipitation sequencing (meRIP-seq). Levels of host factors involved in m6A installation, removal, and recognition were unchanged by HCoV-OC43 infection; however, nuclear localization of METTL3 and cytoplasmic m6A readers YTHDF1 and YTHDF2 increased. This establishes that coronavirus RNAs are m6A-modified and host m6A pathway components control ß-coronavirus replication. Moreover, it illustrates the therapeutic potential of targeting the m6A pathway to restrict coronavirus reproduction.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Replicación Viral / Procesamiento Postranscripcional del ARN / Coronavirus Humano OC43 / SARS-CoV-2 Límite: Humans Idioma: En Revista: Genes Dev Asunto de la revista: BIOLOGIA MOLECULAR Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Replicación Viral / Procesamiento Postranscripcional del ARN / Coronavirus Humano OC43 / SARS-CoV-2 Límite: Humans Idioma: En Revista: Genes Dev Asunto de la revista: BIOLOGIA MOLECULAR Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos