title: MCPIP1 ribonuclease antagonizes dicer and terminates microRNA biogenesis through precursor microRNA degradation.
abstract: MicroRNAs (miRNAs) are versatile regulators of gene expression and undergo complex maturation processes. However, the mechanism(s) stabilizing or reducing these small RNAs remains poorly understood. Here we identify mammalian immune regulator MCPIP1 (Zc3h12a) ribonuclease as a broad suppressor of miRNA activity and biogenesis, which counteracts Dicer, a central ribonuclease in miRNA processing. MCPIP1 suppresses miRNA biosynthesis via cleavage of the terminal loops of precursor miRNAs (pre-miRNAs). MCPIP1 also carries a vertebrate-specific oligomerization domain important for pre-miRNA recognition, indicating its recent evolution. Furthermore, we observed potential antagonism between MCPIP1 and Dicer function in human cancer and found a regulatory role of MCPIP1 in the signaling axis comprising miR-155 and its target c-Maf. These results collectively suggest that the balance between processing and destroying ribonucleases modulates miRNA biogenesis and potentially affects pathological miRNA dysregulation. The presence of this abortive processing machinery and diversity of MCPIP1-related genes may imply a dynamic evolutional transition of the RNA silencing system.
authors: Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors: Hiroshi I
authors: HI
authors: Suzuki
authors: Mayu
authors: M
authors: Arase
authors: Hironori
authors: H
authors: Matsuyama
authors: Young Lim
authors: YL
authors: Choi
authors: Toshihide
authors: T
authors: Ueno
authors: Hiroyuki
authors: H
authors: Mano
authors: Koichi
authors: K
authors: Sugimoto
authors: Kohei
authors: K
authors: Miyazono
mesh_terms: D001483:Base Sequence; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D019169:Jurkat Cells; D035683:MicroRNAs / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics*; D009690:Nucleic Acid Conformation; D055503:Protein Multimerization; D051257:Proto-Oncogene Proteins c-maf / Q000378:metabolism; D034622:RNA Interference; D012322:RNA Precursors / Q000378:metabolism*; D020871:RNA Stability; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism*; D012260:Ribonucleases; D013997:Time Factors; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: C495607:MAF protein, human; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D051257:Proto-Oncogene Proteins c-maf; D012322:RNA Precursors; D014157:Transcription Factors; D012260:Ribonucleases; C510646:ZC3H12A protein, human; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases