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RNA-binding protein HuR regulates hsa-let-7c expression by its RNA recognition motif

Song Yao, FENG Wei, SHI Guo-Min, CHEN Chao, ZHANG YOU-YI ^*

Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that control diverse cellular and developmental events through repression of large sets of target mRNAs. miRNAs expressions were mainly regulated at two levels: transcriptional and post-transcriptional. Transcriptional regulation of miRNA-encoding genes produce specific expression patterns of individual miRNA. However, the mechanism of post-transcriptional regulation of miRNAs remains largely unknown. The present study was aimed to clarify whether HuR, an evolutionary conserved AU-rich binding protein, could regulate miRNAs expressions. By means of a computational screen for AUUUA motifs within pri-miRNAs, we found that the downstream of hsa-let-7c but not hsa-miR-21 was enriched of AUUUA motifs. Then we transfected HuR and mutant HuR lacking RNA recognition motif 3 (RRM3) respectively into HEK293T cells. And HuR protein and miRNAs expressions were detected by Western blot and real-time PCR, respectively. The results showed that the overexpression of HuR promoted mature hsa-let-7c expression but not hsa-miR-21 expression. Furthermore, overexpression of HuR deletion mutant lacking RRM3 did not promote hsa-let-7c expression. These results suggest that RRM3 is crucial for HuR mediating mature hsa-let-7c expression. Collectively, these findings proposed a novel role of HuR in biogenesis of miRNAs, possibly by way of post-transcriptional regulation of miRNAs.

Key words: microRNA; HuR ; let-7c ; post-transcriptional regulation

Received: 2017-03-11　　Accepted: 2018-01-24

Corresponding author: 张幼怡　　E-mail: zhangyy@bjmu.edu.cn

DOI: 10.13294/j.aps.2018.0008

Citing This Article：

Song Yao, FENG Wei, SHI Guo-Min, CHEN Chao, ZHANG YOU-YI . RNA-binding protein HuR regulates hsa-let-7c expression by its RNA recognition motif. Acta Physiol Sin 2018; 70 (1): 1-8