title: Destabilization of microRNAs in human cells by 3' deadenylation mediated by PARN and CUGBP1.
abstract: MicroRNA-122 (miR-122), which is expressed at high levels in hepatocytes, is selectively stabilized by 3'-adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2. Here, we report that poly(A)-specific ribonuclease (PARN) is responsible for the deadenylation and destabilization of miR-122. The 3'-oligoadenylated variant of miR-122 was detected in Huh7 cells when PARN was down-regulated. In addition, both the steady-state level and stability of miR-122 were increased in PARN knockdown cells. We also demonstrate that CUG-binding protein 1 (CUGBP1) specifically interacts with miR-122 and other UG-rich miRNAs, and promotes their destabilization. Overexpression of CUGBP1 or PARN in Huh7 cells reduced the steady-state levels of these miRNAs. Because CUGBP1 interacts directly with PARN, we hypothesized that it specifically recruits PARN to miR-122. In fact, CUGBP1 enhanced PARN-mediated deadenylation and degradation of miR-122 in a dose-dependent manner in vitro. These results indicate that the cellular level of miR-122 is determined by the balance between the opposing effects of GLD-2 and PARN/CUGBP1 on the metabolism of its 3'-terminus.
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Katoh
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hojo
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan ts@chembio.t.u-tokyo.ac.jp.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D060565:Argonaute Proteins / Q000378:metabolism; D000067879:CELF1 Protein / Q000378:metabolism*; D002460:Cell Line; D005095:Exoribonucleases / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000378:metabolism*; D020871:RNA Stability
chemical_list: D060565:Argonaute Proteins; D000067879:CELF1 Protein; D005095:Exoribonucleases; D035683:MicroRNAs; C102843:CELF1 protein, human; C531907:MIRN122 microRNA, human