The micropeptide LEMP plays an evolutionarily conserved role in myogenesis

The micropeptide LEMP plays an evolutionarily conserved role in myogenesis
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微肽 LEMP 在肌生成中发挥进化保守的作用

DOI:
10.1038/s41419-020-2570-5
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发表时间:
2020-05
影响因子:
9
通讯作者:
Cheng Hong
Cheng Hong
中科院分区:
生物学1区
文献类型:
--
作者:
Wang Lantian;Fan Jing;Han Lili;Qi Haonan;Wang Yimin;Wang Hongye;Chen Suli;Du Lei;Li Sheng;Zhang Yunbin;Tang Wei;Ge Gaoxiang;Pan Weijun;Hu Ping;Cheng Hong

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近年来,微肽越来越多地被认为是各种生物过程中的重要调节因子。然而,微肽是否在功能上是保守的在很大程度上还不清楚。在这里,我们发现了一种在肌肉发生中具有进化保守作用的微肽。对增殖的小鼠卫星细胞(SCs)和分化的肌管的RNA-SEQ数据分析发现了一个先前注释的LncRNA,MyolncR4(1500011K16RIK),它在肌肉分化过程中上调。值得注意的是,MyolncR4在脊椎动物中高度保守。多条证据表明,MyolncR4编码一个56个氨基酸的微肽,命名为LEMP(lncRNA编码的微肽)。LEMP可促进小鼠肌肉的形成和再生。在斑马鱼中,MyolncR4富含发育中的体节,消除LEMP会导致肌肉发育受损,而表达小鼠LEMP可以有效地挽救肌肉发育。有趣的是,LEMP同时定位于质膜和线粒体,并与多种线粒体蛋白相关,提示它参与了线粒体功能。总而言之,我们的工作揭示了一种在骨骼肌分化中扮演进化保守角色的微肽,明确了这一不断增长的小肽家族的功能重要性。
In recent years, micropeptides have been increasingly identified as important regulators in various biological processes. However, whether micropeptides are functionally conserved remains largely unknown. Here, we uncovered a micropeptide with evolutionarily conserved roles in myogenesis. RNA-seq data analysis of proliferating mouse satellite cells (SCs) and differentiated myotubes identified a previously annotated lncRNA, MyolncR4 (1500011K16RIK), which is upregulated during muscle differentiation. Significantly, MyolncR4 is highly conserved across vertebrate species. Multiple lines of evidence demonstrate that MyolncR4 encodes a 56-aa micropeptide, which was named as LEMP (lncRNA encoded micropeptide). LEMP promotes muscle formation and regeneration in mouse. In zebrafish, MyolncR4 is enriched in developing somites and elimination of LEMP results in impaired muscle development, which could be efficiently rescued by expression of the mouse LEMP. Interestingly, LEMP is localized at both the plasma membrane and mitochondria, and associated with multiple mitochondrial proteins, suggestive of its involvement in mitochondrial functions. Together, our work uncovers a micropeptide that plays an evolutionarily conserved role in skeletal muscle differentiation, pinpointing the functional importance of this growing family of small peptides.
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