Tweet
Cell Host Microbe. 2017 Sep 13;22(3):377-386.e5. doi: 10.1016/j.chom.2017.08.004.
Epitranscriptomic Enhancement of Influenza A Virus Gene Expression and Replication.
Courtney DG1, Kennedy EM1, Dumm RE1, Bogerd HP1, Tsai K1, Heaton NS1, Cullen BR2.
Author information
Abstract
Many viral RNAs are modified by methylation of the N6 position of adenosine (m6A). m6A is thought to regulate RNA splicing, stability, translation, and secondary structure. Influenza A virus (IAV) expresses m6A-modified RNAs, but the effects of m6A on this segmented RNA virus remain unclear. We demonstrate that global inhibition of m6A addition inhibits IAV gene expression and replication. In contrast, overexpression of the cellular m6A "reader" protein YTHDF2 increases IAV gene expression and replication. To address whether m6A residues modulate IAV RNA function in cis, we mapped m6A residues on the IAV plus (mRNA) and minus (vRNA) strands and used synonymous mutations to ablate m6A on both strands of the hemagglutinin (HA) segment. These mutations inhibited HA mRNA and protein expression while leaving other IAV mRNAs and proteins unaffected, and they also resulted in reduced IAV pathogenicity in mice. Thus, m6A residues in IAV transcripts enhance viral gene expression.
Copyright ? 2017 Elsevier Inc. All rights reserved.
KEYWORDS:
RNA methylation; YTHDF2; epitranscriptomics; influenza A virus; m(6)A; mRNA function; post-transcriptional regulation; viral pathogenesis
PMID: 28910636 DOI: 10.1016/j.chom.2017.08.004
Epitranscriptomic Enhancement of Influenza A Virus Gene Expression and Replication.
Courtney DG1, Kennedy EM1, Dumm RE1, Bogerd HP1, Tsai K1, Heaton NS1, Cullen BR2.
Author information
Abstract
Many viral RNAs are modified by methylation of the N6 position of adenosine (m6A). m6A is thought to regulate RNA splicing, stability, translation, and secondary structure. Influenza A virus (IAV) expresses m6A-modified RNAs, but the effects of m6A on this segmented RNA virus remain unclear. We demonstrate that global inhibition of m6A addition inhibits IAV gene expression and replication. In contrast, overexpression of the cellular m6A "reader" protein YTHDF2 increases IAV gene expression and replication. To address whether m6A residues modulate IAV RNA function in cis, we mapped m6A residues on the IAV plus (mRNA) and minus (vRNA) strands and used synonymous mutations to ablate m6A on both strands of the hemagglutinin (HA) segment. These mutations inhibited HA mRNA and protein expression while leaving other IAV mRNAs and proteins unaffected, and they also resulted in reduced IAV pathogenicity in mice. Thus, m6A residues in IAV transcripts enhance viral gene expression.
Copyright ? 2017 Elsevier Inc. All rights reserved.
KEYWORDS:
RNA methylation; YTHDF2; epitranscriptomics; influenza A virus; m(6)A; mRNA function; post-transcriptional regulation; viral pathogenesis
PMID: 28910636 DOI: 10.1016/j.chom.2017.08.004