Inhibition of Human BK Polyomavirus Replication by Small Noncoding RNAs

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Title: Inhibition of Human BK Polyomavirus Replication by Small Noncoding RNAs
Authors: Tikhanovich, I.
Liang, B.
Seoighe, C.
et al.
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Date: 4-May-2011
Abstract: Small noncoding RNAs regulate a variety of cellular processes, including genomic imprinting, chromatin remodeling, replication, transcription, and translation. Here, we report small replication-regulating RNAs (srRNAs) that specifically inhibit DNA replication of the human BK polyomavirus (BKV) in vitro and in vivo. srRNAs from FM3A murine mammary tumor cells were enriched by DNA replication assay-guided fractionation and hybridization to the BKV noncoding control region (NCCR) and synthesized as cDNAs. Selective mutagenesis of the cDNA sequences and their putative targets suggests that the inhibition of BKV DNA replication is mediated by srRNAs binding to the viral NCCR, hindering early steps in the initiation of DNA replication. Ectopic expression of srRNAs in human cells inhibited BKV DNA replication in vivo. Additional srRNAs were designed and synthesized that specifically inhibit simian virus 40 (SV40) DNA replication in vitro. These observations point to novel mechanisms for regulating DNA replication and suggest the design of synthetic agents for inhibiting replication of polyomaviruses and possibly other viruses.
Type of material: Journal Article
Publisher: American Society for Microbiology
Journal: Journal of Virology
Volume: 85
Issue: 14
Start page: 6930
End page: 6940
Copyright (published version): 2011 American Society for Microbiology
Keywords: BK virus (BKV)small replication-regulating RNAs (srRNAs)
DOI: 10.1128/JVI.00547-11
Language: en
Status of Item: Peer reviewed
Appears in Collections:SBI Research Collection

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