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

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...

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Published in:Nucleic acids research Vol. 45; no. 11; pp. 6894 - 6910
Main Authors: Lee, Hyung Chul, Jung, Seung Hee, Hwang, Hyun Jung, Kang, Donghee, De, Supriyo, Dudekula, Dawood B., Martindale, Jennifer L., Park, Byungkyu, Park, Seung Kuk, Lee, Eun Kyung, Lee, Jeong-Hwa, Jeong, Sunjoo, Han, Kyungsook, Park, Heon Joo, Ko, Young-Gyu, Gorospe, Myriam, Lee, Jae-Seon
Format: Journal Article
Language:English
Published: England Oxford University Press 20.06.2017
Subjects:
3' Untranslated Regions
Argonaute Proteins - physiology
Base Sequence
Binding Sites
Carrier Proteins - physiology
Eukaryotic Initiation Factors - metabolism
HCT116 Cells
HEK293 Cells
Humans
Inverted Repeat Sequences
MCF-7 Cells
MicroRNAs - physiology
Nuclear Proteins - physiology
Protein Binding
Protein Biosynthesis
Protein Domains
RNA
RNA Interference
RNA Stability
RNA, Messenger - genetics
RNA, Messenger - metabolism
RNA-Binding Proteins
ISSN:0305-1048, 1362-4962, 1362-4962
Online Access:Get full text
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Summary: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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ISSN:0305-1048
1362-4962
1362-4962
DOI:10.1093/nar/gkx307