DOI . ORG {
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We began analyzing https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006919, but it redirected us to https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006919. The analysis below is for the second page.
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Author summary All organisms, including all viruses, use mRNAs to express the proteins required for their viability and replication. Viruses, in particular, are under pressure to replicate rapidly in order to spread before the host immune response becomes effective. Previously, it was reported that several viruses, including polyomaviruses, express mRNAs that bear methylated adenosine (m6A) residues, but the functional relevance of this modification was unclear. Here, we demonstrate that addition of m6A to mRNAs encoded by the prototypic polyomavirus SV40 increases both viral structural protein expression and viral spread. Targeting the sites of addition of m6A on SV40 mRNAs, using mutagenesis, therefore reduces SV40 replication, and a drug that globally inhibits m6A addition has a similar effect. These data identify m6A addition as a key step, and potential Achilles heel, in the polyomavirus life cycle.
Title[redir]:
No title found...
Description:
Author summary All organisms, including all viruses, use mRNAs to express the proteins required for their viability and replication. Viruses, in particular, are under pressure to replicate rapidly in order to spread before the host immune response becomes effective. Previously, it was reported that several viruses, including polyomaviruses, express mRNAs that bear methylated adenosine (m6A) residues, but the functional relevance of this modification was unclear. Here, we demonstrate that addition of m6A to mRNAs encoded by the prototypic polyomavirus SV40 increases both viral structural protein expression and viral spread. Targeting the sites of addition of m6A on SV40 mRNAs, using mutagenesis, therefore reduces SV40 replication, and a drug that globally inhibits m6A addition has a similar effect. These data identify m6A addition as a key step, and potential Achilles heel, in the polyomavirus life cycle.
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Keywords {🔍}
cells, fig, ythdf, bsc, viral, expression, replication, virus, sites, vpm, cell, article, late, view, google, scholar, addition, gene, region, mutant, pmid, pubmedncbi, protein, infected, rna, mrna, transcripts, observed, type, control, mrnas, wild, level, viruses, early, mutations, western, blot, data, reported, genome, previously, residues, mettl, effect, nuclear, shown, peak, plaques, infection,
Topics {✒️}
health grants r21-ai130574 s-adenosyl-l-homocysteine hydrolase inhibitor plos pathog 14 cookies plos plasmid expressing glutathione-s-transferase mutation validation pa-m6a-seq human polyomavirus diseases vpm pa-m6a-seq runs photo-crosslinking-assisted m6a sequencing overexpress flag-tagged versions pgem-sv40 kpni-kpni fragment epitope-tagged ythdf proteins photoactivatable ribonucleoside-enhanced crosslinking m6a mutant pk-flag-vpm nih grant t32-ca009111 gonzales-van horn sr synaptic systems synaptic systems 202–003 gfp-expressing bsc40 cells pa-m6a-seq procedure bsc40/ythdf2 cell line resulting pgem-sv40 plasmid larger viral plaques multiple pa-m6a-seq larger ythdf3 protein y2/y3 par-clip experiments transcriptional n6-adenosine methylation flag-tagged version 5x serum-free dmem original author ythdf2-overexpressing bsc40 cells including pathogenic polyomaviruses promotes cap-independent translation pgem-sv40-vpm plasmid s-adenosyl homocysteine cellular protein β-actin abstract polyomaviruses key m6a reader sequence alignment/map format n6-methyladenosine-modified rna n6-methyladenosine methylated mrnas kpni digested pgem-sv40 /kits/mtt-assay-protocol commercial ythdf2-specific antiserum cross-linked 4su residues m6a-mutant virus vpm crosslinked complex global inhibitor accessible data icon photo-crosslinking-assisted
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