The developmental transcriptome sequencing of bovine skeletal muscle reveals a long noncoding RNA, lncMD, promotes muscle differentiation by sponging miR-125b
The developmental transcriptome sequencing of bovine skeletal muscle reveals a long noncoding RNA, lncMD, promotes muscle differentiation by sponging miR-125b
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牛骨骼肌发育转录组测序揭示长非编码 RNA lncMD 通过海绵 miR-125b 促进肌肉分化
DOI：
10.1016/j.bbamcr.2016.08.014
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发表时间：
2016-11-01
影响因子：
5.1
通讯作者：
Chen, Hong
中科院分区：
文献类型：
--
作者：
Sun, Xiaomei;Li, Mingxun;Chen, Hong
哺乳动物基因组的普遍转录产生大量的长链非编码RNA（lncRNA），其在多种生物过程中至关重要。高通量测序技术的最新进展有助于加快IncRNA发现的步伐。然而，还没有关于肌肉发育过程中lncRNA的总体表达模式的研究。我们在这里报道了使用Ribo-Zero RNA-Seq首次分析牛胚胎，新生儿和成年骨骼肌中的IncRNA景观，该技术可以捕获poly（A）和poly（A）-转录本。我们最终确定了7692个高置信度的IncRNA，并发现了401个在三个发育阶段中差异表达的IncRNA，包括lncMD，一种新的肌肉特异性IncRNA，在成肌细胞分化过程中逐渐上调。lncMD过表达上调，而lncMD沉默降低了两个成熟的肌生成标记物，肌球蛋白重链（MHC）和肌生成素（MyoG）的表达。深入分析表明，lncMD作为miR-125 b的分子海绵，胰岛素样生长因子2（IGF 2）是牛中miR-125 b的直接靶点。此外，在牛肌肉组织中，lncMD水平与IGF 2 mRNA水平正相关，这是ceRNA功能的重要推论。总而言之，我们的研究表明，lncMD作为ceRNA螯合miR-125 b，导致IGF 2表达增加，从而促进肌肉分化。我们的研究结果也补充了牛的参考基因组注释，这可能有助于进一步的功能性IncRNA克隆和更全面的研究肌肉发育中的IncRNA调控。(C)2016爱思唯尔B. V.保留所有权利。
Pervasive transcription of the mammalian genome generates numerous long noncoding RNAs (lncRNAs), which are of crucial importance in diverse biological processes. Recent advances in high throughput sequencing technology have helped to accelerate the pace of IncRNA discovery. However, no study on the overall expression patterns of lncRNAs during muscle development has been conducted. We reported here the first analysis of IncRNA landscape in bovine embryonic, neonatal and adult skeletal muscle using Ribo-Zero RNA-Seq, a technology which can capture both poly(A) and poly(A)-transcripts. We finally defined 7692 high-confidence IncRNAs and uncovered 401 lncRNAs differentially expressed among three developmental stages, including lncMD, a novel muscle-specific IncRNA which is gradually up-regulated during myoblast differentiation. lncMD overexpression upregulated, whereas lncMD silencing decreased the expression of two well-established myogenic markers, myosin heavy chain (MHC) and myogenin (MyoG). In-depth analyses showed that lncMD acts as a molecular sponge for miR-125b and that insulin-like growth factor 2 (IGF2) is a direct target of miR-125b in cattle. Moreover, lncMD level was positively correlated with IGF2 mRNA level in bovine muscle tissues, a vital corollary to ceRNA function. Altogether, our research showed that lncMD acts as a ceRNA to sequester miR-125b, leading to heightened IGF2 expression and thus promotes muscle differentiation. Our findings also complement the reference genome annotation of cattle, which will likely be useful for further functional IncRNA cloning and more comprehensive studies on IncRNA regulation in muscle development. (C) 2016 Elsevier B.V. All rights reserved.