title: Selective degradation of host MicroRNAs by an intergenic HCMV noncoding RNA accelerates virus production.
abstract: Virulence of human cytomegalovirus (HCMV) clinical isolates correlates with carriage of a 15 kb segment in the UL/b' region of the viral genome, which is absent from attenuated strains. The mechanisms by which this segment contributes to HCMV virulence remain obscure. We observed that intergenic RNA sequences within the 15 kb segment function as a microRNA (miRNA) decay element (miRDE) and direct the selective, sequence-specific turnover of mature miR-17 and miR-20a encoded within the host miR-17-92 cluster. Unlike canonical miRNA-mRNA interactions, the miRNA-miRDE interactions did not repress miRDE expression. miRNA binding site mutations retargeted miRDE to other miR-17-92 cluster miRNAs, which are otherwise resistant to miRDE-mediated decay. miRDE function was required to accelerate virus production in the context of lytic HCMV infection. These results indicate a role for viral noncoding RNA in regulating cellular miRNAs during HCMV pathogenesis and suggest that noncoding RNAs may play a role in mature miRNA turnover.
authors.affiliation: National Creative Research Initiatives Center for Antigen Presentation, Seoul 151-747, Republic of Korea.
authors.forename: Sanghyun
authors.initials: S
authors.lastname: Lee
authors.forename: Jaewon
authors.initials: J
authors.lastname: Song
authors.forename: Sungchul
authors.initials: S
authors.lastname: Kim
authors.forename: Jongkyu
authors.initials: J
authors.lastname: Kim
authors.forename: Yujin
authors.initials: Y
authors.lastname: Hong
authors.forename: Youngkyun
authors.initials: Y
authors.lastname: Kim
authors.forename: Donghyun
authors.initials: D
authors.lastname: Kim
authors.forename: Daehyun
authors.initials: D
authors.lastname: Baek
authors.forename: Kwangseog
authors.initials: K
authors.lastname: Ahn
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D003587:Cytomegalovirus / Q000502:physiology*; D004252:DNA Mutational Analysis; D021901:DNA, Intergenic; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D020871:RNA Stability; D012367:RNA, Viral / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D021901:DNA, Intergenic; C524941:MIRN17 microRNA, human; C534451:MIRN20a microRNA, human; D035683:MicroRNAs; D012367:RNA, Viral