Sirt1 AS lncRNA interacts with its mRNA to inhibit muscle formation by attenuating function of miR-34a

• Published in: Scientific reports Vol. 6; no. 1; p. 21865
• Main Authors: Wang, Guo-qiang, Wang, Yu, Xiong, Yan, Chen, Xiao-Chang, Ma, Mei-ling, Cai, Rui, Gao, Yun, Sun, Yun-mei, Yang, Gong-She, Pang, Wei-Jun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.02.2016; Nature Publishing Group
• Subjects: 13/109; 13/31; 13/44; 3' Untranslated regions; 38/39; 38/77; 631/337/384; 631/80/83; 64/60; 82/80; Animals; Antisense RNA; Base Sequence; Body fat; Body Weight; Cell Differentiation; Cell Line; Cell Proliferation; Cytoplasm; Gene expression; Gene Expression Regulation, Developmental; Genes, Reporter; Humanities and Social Sciences; Luciferases - genetics; Luciferases - metabolism; Mice; Mice, Inbred C57BL; MicroRNAs - genetics; MicroRNAs - metabolism; mRNA stability; multidisciplinary; Muscle Development - genetics; Myoblasts - cytology; Myoblasts - metabolism; Myogenesis; Nucleic Acid Conformation; Protein Biosynthesis; Ribonuclease; RNA Stability; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Science; Signal Transduction; SIRT1 protein; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; Transcription; Transcription, Genetic
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep21865

Recent studies demonstrate the functions of long non-coding RNAs (lncRNAs) in mediating gene expression at the transcriptional or translational level. Our previous study identified a Sirt1 antisense (AS) lncRNA transcribed from the Sirt1 AS strand. However, its role and regulatory mechanism is still unknown in myogenesis. Here, functional analyses showed that Sirt1 AS lncRNA overexpression promoted myoblast proliferation, but inhibited differentiation. Mechanistically, Sirt1 AS lncRNA was found to activate its sense gene, Sirt1 . The luciferase assay provided evidences that Sirt1 AS lncRNA interacted with Sirt1 3′ UTR and rescued Sirt1 transcriptional suppression by competing with miR-34a. In addition, RNA stability assay showed that Sirt1 AS lncRNA prolonged Sirt1 mRNA half-life from 2 to 10 h. Ribonuclease protection assay further indicated that it fully bound to Sirt1 mRNA in the myoblast cytoplasm. Moreover, Sirt1 AS overexpression led to less mouse weight than the control because of less lean mass and greater levels of Sirt1 , whereas the fat mass and levels of miR-34a were not altered. Based on the findings, a novel regulatory mechanism was found that Sirt1 AS lncRNA preferably interacted with Sirt1 mRNA forming RNA duplex to promote Sirt1 translation by competing with miR-34a, inhibiting muscle formation.