Long noncoding RNA SMUL suppresses SMURF2 production-mediated muscle atrophy via nonsense-mediated mRNA decay.
Long noncoding RNA SMUL suppresses SMURF2 production-mediated muscle atrophy via nonsense-mediated mRNA decay.
复制标题
长非编码 RNA SMUL 通过无义介导的 mRNA 衰减抑制 SMURF2 产生介导的肌肉萎缩
DOI：
10.1016/j.omtn.2020.12.003
复制
发表时间：
2021-03-05
期刊：
影响因子：
--
通讯作者：
Nie Q
中科院分区：
文献类型：
--
作者：
Cai B;Li Z;Ma M;Zhang J;Kong S;Abdalla BA;Xu H;Jebessa E;Zhang X;Lawal RA;Nie Q
随着世界人口的增长，肌肉萎缩导致的肌肉萎缩可能会成为更大的风险。已知长链非编码rna （lncRNAs）在肌肉生长和肌肉萎缩中起重要作用。与此同时，最近发现许多假定的小开放阅读框架（sorf）隐藏在lncrna中；然而，它们的翻译能力和功能尚不清楚。在这项研究中，我们通过整合转录组学和蛋白质组学分析发现了104个与肌生成相关的lncrna，至少在一个小肽中被翻译。此外，我们构建了ORF （uORF）上游调控网络，并鉴定了一种名为SMUL （Smad ubiquitin regulatory factor 2 [SMURF2] upstream lncRNA）的新型肌萎缩相关lncRNA。SMUL在骨骼肌中高表达，在成肌细胞分化过程中表达水平下调。SMUL促进成肌细胞增殖，抑制体外分化。在体内，SMUL诱导骨骼肌萎缩，并促进从慢肌纤维到快肌纤维的转换。同时，SMUL sORF的翻译破坏了SMURF2 mRNA的稳定性。机制上，SMUL通过无义介导的mRNA衰变（NMD）抑制SMURF2的产生，参与调控转化生长因子β (TGF-β)/SMAD通路，进而调控肌肉发生和肌肉萎缩。综上所述，这些结果表明SMUL可能是肌肉萎缩的一种新的治疗靶点。肌肉萎缩已经成为一个主要的健康挑战。Nie及其同事发现了一种新的lncRNA SMUL，它通过无义介导的mRNA衰变来抑制SMURF2的产生，从而调节肌肉发生并诱导肌肉萎缩，这表明SMUL可能作为肌肉萎缩的潜在治疗靶点。
As the world population grows, muscle atrophy leading to muscle wasting could become a bigger risk. Long noncoding RNAs (lncRNAs) are known to play important roles in muscle growth and muscle atrophy. Meanwhile, it has recently come to light that many putative small open reading frames (sORFs) are hidden in lncRNAs; however, their translational capabilities and functions remain unclear. In this study, we uncovered 104 myogenic-associated lncRNAs translated, in at least a small peptide, by integrated transcriptome and proteomic analyses. Furthermore, an upstream ORF (uORF) regulatory network was constructed, and a novel muscle atrophy-associated lncRNA named SMUL (Smad ubiquitin regulatory factor 2 [SMURF2] upstream lncRNA) was identified. SMUL was highly expressed in skeletal muscle, and its expression level was downregulated during myoblast differentiation. SMUL promoted myoblast proliferation and suppressed differentiation in vitro. In vivo, SMUL induced skeletal muscle atrophy and promoted a switch from slow-twitch to fast-twitch fibers. In the meantime, translation of the SMUL sORF disrupted the stability of SMURF2 mRNA. Mechanistically, SMUL restrained SMURF2 production via nonsense-mediated mRNA decay (NMD), participating in the regulation of the transforming growth factor β (TGF-β)/SMAD pathway and further regulating myogenesis and muscle atrophy. Taken together, these results suggest that SMUL could be a novel therapeutic target for muscle atrophy. Muscle atrophy has become a major health challenge. Nie and colleagues identified a novel lncRNA, SMUL, that restrains SMURF2 production via nonsense-mediated mRNA decay to modulate myogenesis and induce muscle atrophy, suggesting that SMUL may serve as a potential therapeutic target for muscle atrophy.
登录
查看更多内容
影响因子：
3.3
作者：
Cao S;Xiao L;Rao JN;Zou T;Liu L;Zhang D;Turner DJ;Gorospe M;Wang JY
通讯作者：
Wang JY
影响因子：
4.3
作者：
Dinger ME;Pang KC;Mercer TR;Mattick JS
通讯作者：
Mattick JS
影响因子：
10.5
作者：
Cabili, Moran N.;Trapnell, Cole;Rinn, John L.
通讯作者：
Rinn, John L.
影响因子：
3.5
作者：
Cai, Yu;Zhou, Chao Hui;Shen, Xi Zhong
通讯作者：
Shen, Xi Zhong
影响因子：
3.5
作者：
Iacono, M;Mignone, F;Pesole, G
通讯作者：
Pesole, G