Regulation of Human RNase-L by the miR-29 Family Reveals a Novel Oncogenic Role in Chronic Myelogenous Leukemia

The endoribonuclease RNase-L is the terminal component of an interferon-regulated RNA decay pathway known as the 2′-5′-oligoadenylate (2–5A) system, whose established functions include antimicrobial and tumor suppressive activities. RNase-L activity requires binding of the small molecule 2–5A, leading to RNase-L dimerization and cleavage of single-stranded RNA. RNase-L expression is controlled post-transcriptionally by its 3′-untranslated region (3′ UTR), which exerts a strong negative effect on RNase-L levels. MicroRNAs (miRNAs) are a class of small noncoding RNAs that repress expression of target genes by binding to regions of complementarity often in the 3′ UTR. The miR-29 family acts as a tumor suppressor in several cancers, including acute and chronic myelogenous leukemia (CML), and has many oncogenic targets. We report that the miR-29 family represses RNase-L protein expression across several cell types. Using a luciferase reporter, we showed that miR-29 acts via 4 target sites within the RNASEL 3′ ...