microRNAs are fine-tuners of gene expression and play important roles in various pathophysiological processes. In mammalian microRNA biogenesis, microRNA precursors are processed to mature microRNAs through cleavage by two ribonucleases, Drosha and Dicer; however, the mechanism(s) reducing microRNAs remains poorly understood. Suzuki et al. from Miyazono's Lab identified mammalian immune regulator MCPIP1 (Zc3h12a) ribonuclease as a novel broad suppressor of microRNA activity and biogenesis. MCPIP1 ribonuclease suppresses microRNA biosynthesis via cleavage of the terminal loops of microRNA precursors and counteracts Dicer. This study proposes a novel concept that the balance between processing and destructing ribonucleases modulates microRNA biogenesis and potentially affects pathological microRNA dysregulation. They also observed functional antagonism between MCPIP1 and Dicer function in human cancer transcriptome. These findings will greatly contribute to clarify the roles of microRNAs in various diseases and advance the development of RNA-based diagnostic tools and therapeutics.

Program member
Kohei Miyazono (Department of Molecular Pathology, Graduate School of Medicine)

Regulation of microRNA biogenesis by Drosha, Dicer and MCPIP1.