Interplay between coronavirus, a cytoplasmic RNA virus, and nonsense-mediated mRNA decay pathway

Masami Wada, Kumari G. Lokugamage, Keisuke Nakagawa, Krishna Narayanan, Shinji Makino

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Coronaviruses (CoVs), including severe acute respiratory syndrome CoV and Middle East respiratory syndrome CoV, are enveloped RNA viruses that carry a large positive-sense single-stranded RNA genome and cause a variety of diseases in humans and domestic animals. Very little is known about the host pathways that regulate the stability of CoV mRNAs, which carry some unusual features. Nonsense-mediated decay (NMD) is a eukaryotic RNA surveillance pathway that detects mRNAs harboring aberrant features and targets them for degradation. Although CoV mRNAs are of cytoplasmic origin, the presence of several NMD-inducing features (including multiple ORFs with internal termination codons that create a long 3' untranslated region) in CoV mRNAs led us to explore the interplay between the NMD pathway and CoVs. Our study using murine hepatitis virus as a model CoV showed that CoV mRNAs are recognized by the NMD pathway as a substrate, resulting in their degradation. Furthermore, CoV replication induced the inhibition of the NMD pathway, and N protein (a viral structural protein) had an NMD inhibitory function that protected viral mRNAs from rapid decay. Our data further suggest that the NMD pathway interferes with optimal viral replication by degrading viral mRNAs early in infection, before sufficient accumulation of N protein. Our study presents clear evidence for the biological importance of the NMD pathway in controlling the stability of mRNAs and the efficiency of replication of a cytoplasmic RNA virus.

Original languageEnglish (US)
Pages (from-to)E10157-E10166
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number43
DOIs
StatePublished - Oct 23 2018

Fingerprint

Nonsense Mediated mRNA Decay
Coronavirus
RNA Viruses
RNA Stability
Messenger RNA
Coronavirus Infections
RNA
Murine hepatitis virus
Viral Structural Proteins
Severe Acute Respiratory Syndrome
Terminator Codon
Domestic Animals
3' Untranslated Regions
Open Reading Frames
Genome
Infection
Proteins

Keywords

  • Coronavirus
  • Cytoplasmic RNA virus
  • Inhibition of NMD
  • Long 3' UTR
  • Nonsense-mediated mRNA decay

ASJC Scopus subject areas

  • General

Cite this

Interplay between coronavirus, a cytoplasmic RNA virus, and nonsense-mediated mRNA decay pathway. / Wada, Masami; Lokugamage, Kumari G.; Nakagawa, Keisuke; Narayanan, Krishna; Makino, Shinji.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, No. 43, 23.10.2018, p. E10157-E10166.

Research output: Contribution to journalArticle

Wada, Masami ; Lokugamage, Kumari G. ; Nakagawa, Keisuke ; Narayanan, Krishna ; Makino, Shinji. / Interplay between coronavirus, a cytoplasmic RNA virus, and nonsense-mediated mRNA decay pathway. In: Proceedings of the National Academy of Sciences of the United States of America. 2018 ; Vol. 115, No. 43. pp. E10157-E10166.
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