长链非编码RNAH19对哺乳动物肌肉生长发育的调控

摘要

作为最早被鉴定的长链非编码RNA(long non-coding RNA,lncRNA)之一,H19在动物机体内发挥着广泛的作用,不仅可以作为肿瘤抑制因子和致癌基因参与疾病的发生过程,还参与对哺乳动物胚胎各组织生长发育的调控.其中,H19对哺乳动物肌肉组织(包括骨骼肌和心肌)发育的调控受到广泛关注.目前研究发现,H19可通过顺式调控Igf2促进骨骼肌卫星细胞(skeletal muscle satellite cells,SMSCs)的成肌分化和肌肉的生成;H19也可反式作用于靶标基因参与肌肉生长发育过程,如作为“分子海绵”结合let-7、miR-106、miR-29等,影响肌肉细胞中葡萄糖的摄取、心肌细胞增殖和肌腱修复等过程,或作为染色质修饰因子结合MBD1蛋白促进胚胎发育和肌肉再生.本文综述了H19对哺乳动物肌肉生长发育调控的研究进展,以期为进一步阐明肌肉生长发育的分子调控机制提供参考.%As one of the first identified long non-coding RNAs (lncRNAs),H19 plays a wide range of roles in vivo,including not only as a tumor suppressor and oncogene involved in disease process,but also as a regulator of growth and development of multiple tissues in mammalian embryos.The function of H19 in muscles (both skeletal and cardiac muscle)draws widespread attention due to the following two reasons.On one hand,H19 promotes myogenic differentiation and myogenesis of skeletal muscle satellite cells (SMSCs) via regulating Igf2 in cis.On the other hand,H19 also modulates the target genes in trans,including sponging let-7,miR-106 or miR-29 to mediate myocyte glucose uptake,cardiomyocyte proliferation and tendon repair,as well as promote embryonic development and muscle regeneration through binding to MBD1 as a chromatin modifier.In this review,we summarize the role of H19 in mammalian muscles,which will provide a reference for further research to unveil the molecular mechanism of muscle growth and development.