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Nucleic Acids Res. 2017 Jun 20;45(11):6894-6910. doi: 10.1093/nar/gkx307.

WIG1 is crucial for AGO2-mediated ACOT7 mRNA silencing via miRNA-dependent and -independent mechanisms.

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Department of Molecular Medicine, Medical Research Center, Inha University College of Medicine, Incheon 22212, Korea.
Medical Research Center, Inha University College of Medicine, Incheon 22212, Korea.
Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA.
Department of Computer Science and Engineering, Inha University, Incheon 22212, Korea.
Department of Molecular Biology, Dankook University, Yongin 16890, Korea.
Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
Department of Microbiology, Inha University College of Medicine, Incheon 22212, Korea.
Division of Life Sciences, Korea University, Seoul 02841, Korea.


RNA-binding proteins (RBPs) are involved in mRNA splicing, maturation, transport, translation, storage and turnover. Here, we identified ACOT7 mRNA as a novel target of human WIG1. ACOT7 mRNA decay was triggered by the microRNA miR-9 in a WIG1-dependent manner via classic recruitment of Argonaute 2 (AGO2). Interestingly, AGO2 was also recruited to ACOT7 mRNA in a WIG1-dependent manner in the absence of miR-9, which indicates an alternative model whereby WIG1 controls AGO2-mediated gene silencing. The WIG1-AGO2 complex attenuated translation initiation via an interaction with translation initiation factor 5B (eIF5B). These results were confirmed using a WIG1 tethering system based on the MS2 bacteriophage coat protein and a reporter construct containing an MS2-binding site, and by immunoprecipitation of WIG1 and detection of WIG1-associated proteins using liquid chromatography-tandem mass spectrometry. We also identified WIG1-binding motifs using photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation analyses. Altogether, our data indicate that WIG1 governs the miRNA-dependent and the miRNA-independent recruitment of AGO2 to lower the stability of and suppress the translation of ACOT7 mRNA.

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