title: Inhibition of human BK polyomavirus replication by small noncoding RNAs.
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.
authors.affiliation: Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland, Galway, Galway, Ireland.
authors.forename: Irina
authors.initials: I
authors.lastname: Tikhanovich
authors.forename: Bo
authors.initials: B
authors.lastname: Liang
authors.forename: Cathal
authors.initials: C
authors.lastname: Seoighe
authors.forename: William R
authors.initials: WR
authors.lastname: Folk
authors.forename: Heinz Peter
authors.initials: HP
authors.lastname: Nasheuer
mesh_terms: D000818:Animals; D001739:BK Virus / Q000502:physiology*; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D017931:DNA Primers; D004261:DNA Replication; D004279:DNA, Viral / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D051379:Mice; D022661:RNA, Untranslated; D014779:Virus Replication
chemical_list: D017931:DNA Primers; D004279:DNA, Viral; D022661:RNA, Untranslated