Kyung-Won Min, Myung Hyun Jo, Minseok Song, Ji Won Lee, Min Ji Shim, Kyungmin Kim, Hyun Bong Park, Shinwon Ha, Hyejin Mun, Ahsan Polash, Markus Hafner, Jung-Hyun Cho, Dongsan Kim, Ji-Hoon Jeong, Seungbeom Ko, Sungchul Hohng, Sung-Ung Kang, Je-Hyun Yoon
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引用次数: 0
Abstract
Although Argonaute (AGO) proteins have been the focus of microRNA (miRNA) studies, we observed AGO-free mature miRNAs directly interacting with RNA-binding proteins, implying the sophisticated nature of fine-tuning gene regulation by miRNAs. To investigate microRNA-binding proteins (miRBPs) globally, we analyzed PAR-CLIP data sets to identify RBP quaking (QKI) as a novel miRBP for let-7b. Potential existence of AGO-free miRNAs were further verified by measuring miRNA levels in genetically engineered AGO-depleted human and mouse cells. We have shown that QKI regulates miRNA-mediated gene silencing at multiple steps, and collectively serves as an auxiliary factor empowering AGO2/let-7b-mediated gene silencing. Depletion of QKI decreases interaction of AGO2 with let-7b and target mRNA, consequently controlling target mRNA decay. This finding indicates that QKI is a complementary factor in miRNA-mediated mRNA decay. QKI, however, also suppresses the dissociation of let-7b from AGO2, and slows the assembly of AGO2/miRNA/target mRNA complexes at the single-molecule level. We also revealed that QKI overexpression suppresses cMYC expression at post-transcriptional level, and decreases proliferation and migration of HeLa cells, demonstrating that QKI is a tumour suppressor gene by in part augmenting let-7b activity. Our data show that QKI is a new type of RBP implicated in the versatile regulation of miRNA-mediated gene silencing.
期刊介绍:
RNA has played a central role in all cellular processes since the beginning of life: decoding the genome, regulating gene expression, mediating molecular interactions, catalyzing chemical reactions. RNA Biology, as a leading journal in the field, provides a platform for presenting and discussing cutting-edge RNA research.
RNA Biology brings together a multidisciplinary community of scientists working in the areas of:
Transcription and splicing
Post-transcriptional regulation of gene expression
Non-coding RNAs
RNA localization
Translation and catalysis by RNA
Structural biology
Bioinformatics
RNA in disease and therapy