4605

MYBL2

v-myb avian myeloblastosis viral oncogene homolog-like 2;MYBL2;v-myb avian myeloblastosis viral oncogene homolog-like 2

myb-like protein 2|myb-related protein B|v-myb myeloblastosis viral oncogene homolog-like 2

20q13.1

protein-coding

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 3UTR 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 3UTR. In proliferating cells, transfection of miR-29 and miR-30 represses a reporter construct containing the wild-type but not the mutant B-Myb 3UTR, and repression of the mutant 3UTR 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 3UTR and suggest that these microRNAs play an important role in Rb-driven cellular senescence.