Down-regulation of a host microRNA by a Herpesvirus saimiri noncoding RNA.
T cells transformed by Herpesvirus saimiri express seven viral U-rich noncoding RNAs of unknown function called HSURs. We noted that conserved sequences in HSURs 1 and 2 constitute potential binding sites for three host-cell microRNAs (miRNAs). Coimmunoprecipitation experiments confirmed that HSURs 1 and 2 interact with the predicted miRNAs in virally transformed T cells. The abundance of one of these miRNAs, miR-27, is dramatically lowered in transformed cells, with consequent effects on the expression of miR-27 target genes. Transient knockdown and ectopic expression of HSUR 1 demonstrate that it directs degradation of mature miR-27 in a sequence-specific and binding-dependent manner. This viral strategy illustrates use of a ncRNA to manipulate host-cell gene expression via the miRNA pathway.
Cazalla
Demián
D
Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
Yario
Therese
T
Steitz
Joan A
JA
Steitz
Joan
J
D000818:Animals; D020029:Base Pairing; D001665:Binding Sites; D002144:Callithrix; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D017124:Conserved Sequence; D015536:Down-Regulation; D006567:Herpesvirus 2, Saimiriine / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability; D022661:RNA, Untranslated / Q000737:chemistry / Q000378:metabolism*; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism*; D013601:T-Lymphocytes
C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D022661:RNA, Untranslated; D012367:RNA, Viral