Department of Medicine; Program in Molecular Medicine; RNA Therapeutics Institute
Biochemistry | Virology
Influenza A virus (IAV) lacks the enzyme for adding 5' caps to its RNAs and snatches the 5' ends of host capped RNAs to prime transcription. Neither the preference of the host RNA sequences snatched nor the effect of cap-snatching on host processes is completely defined. Previous studies of influenza cap-snatching used poly(A)-selected RNAs from infected cells or relied on annotated host genes to define the snatched host RNAs, and thus lack details on many noncoding host RNAs including snRNAs, snoRNAs, and promoter-associated capped small (cs)RNAs, which are made by "paused" Pol II during transcription initiation. In this study, we used a nonbiased technique, CapSeq, to identify host and viral-capped RNAs including nonpolyadenylated RNAs in the same samples, and investigated the substrate-product correlation between the host RNAs and the viral RNAs. We demonstrated that noncoding host RNAs, particularly U1 and U2, are the preferred cap-snatching source over mRNAs or pre-mRNAs. We also found that csRNAs are highly snatched by IAV. Because the functions of csRNAs remain mostly unknown, especially in somatic cells, our finding reveals that csRNAs at least play roles in the process of IAV infection. Our findings support a model where nascent RNAs including csRNAs are the preferred targets for cap-snatching by IAV and raise questions about how IAV might use snatching preferences to modulate host-mRNA splicing and transcription.
cap-snatching, influenza, noncoding RNA
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© 2015 Gu et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society. This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (seehttp://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
DOI of Published Version
RNA. 2015 Dec;21(12):2067-75. doi: 10.1261/rna.054221.115. Epub 2015 Oct 1. Link to article on publisher's site
RNA (New York, N.Y.)
Gu, Weifeng; Gallagher, Glen R.; Dai, Weiwei; Liu, Ping; Li, Ruidong; Trombly, Melanie I.; Gammon, Don B.; Mello, Craig C.; Wang, Jennifer P.; and Finberg, Robert W., "Influenza A virus preferentially snatches noncoding RNA caps" (2015). University of Massachusetts Medical School Faculty Publications. 849.