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

Hyung Chul Lee, Seung Hee Jung, Hyun Jung Hwang, Donghee Kang, Supriyo De, Dawood B. Dudekula, Jennifer L. Martindale, Byungkyu Park, Seung Kuk Park, Eun Kyung Lee, Jeong Hwa Lee, Sunjoo Jeong, Kyungsook Han, Heon Joo Park, Young-Gyu Ko, Myriam Gorospe, Jae Seon Lee

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)6894-6910
Number of pages17
JournalNucleic Acids Research
Volume45
Issue number11
DOIs
Publication statusPublished - 2017 Jun 1

ASJC Scopus subject areas

  • Genetics

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    Lee, H. C., Jung, S. H., Hwang, H. J., Kang, D., De, S., Dudekula, D. B., Martindale, J. L., Park, B., Park, S. K., Lee, E. K., Lee, J. H., Jeong, S., Han, K., Park, H. J., Ko, Y-G., Gorospe, M., & Lee, J. S. (2017). WIG1 is crucial for AGO2-mediated ACOT7 mRNA silencing via miRNA-dependent and-independent mechanisms. Nucleic Acids Research, 45(11), 6894-6910. https://doi.org/10.1093/nar/gkx307