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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.

SUBMITTER: Katoh T

PROVIDER: S-EPMC4551920 | biostudies-literature |

REPOSITORIES: biostudies-literature

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