title: miR-29 and miR-30 regulate B-Myb expression during cellular senescence.
abstract: Cellular senescence is a form of irreversible growth arrest and a major tumor suppressor mechanism. We show here that the miR-29 and miR-30 microRNA families are up-regulated during induced and replicative senescence and that up-regulation requires activation of the Rb pathway. Expression of a reporter construct containing the 3'UTR of the B-Myb oncogene is repressed during senescence, and repression is blocked by mutations in conserved miR-29 and miR-30 binding sites in the B-Myb 3'UTR. In proliferating cells, transfection of miR-29 and miR-30 represses a reporter construct containing the wild-type but not the mutant B-Myb 3'UTR, and repression of the mutant 3'UTR is reinstituted by compensatory mutations in miR-29 and miR-30 that restore binding to the mutant sites. miR-29 and miR-30 introduction also represses expression of endogenous B-Myb and inhibits cellular DNA synthesis. Finally, interference with miR-29 and miR-30 expression inhibits senescence. These findings demonstrate that miR-29 and miR-30 regulate B-Myb expression by binding to its 3'UTR and suggest that these microRNAs play an important role in Rb-driven cellular senescence.
authors.affiliation: Department of Genetics, Yale School of Medicine, P.O. Box 208005, New Haven, CT 06520, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Martinez
authors.forename: Demian
authors.initials: D
authors.lastname: Cazalla
authors.forename: Laura L
authors.initials: LL
authors.lastname: Almstead
authors.forename: Joan A
authors.initials: JA
authors.lastname: Steitz
authors.forename: Daniel
authors.initials: D
authors.lastname: DiMaio
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D016922:Cellular Senescence; D005347:Fibroblasts / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D012175:Retinoblastoma / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins; C532045:MIRN29a microRNA, human; C546086:MIRN30b microRNA, human; C064352:MYBL2 protein, human; D035683:MicroRNAs; D015534:Trans-Activators