转录组
生物
表型
血管平滑肌
翻译(生物学)
细胞生物学
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真核起始因子
翻译效率
核糖体分析
基因
信使核糖核酸
基因表达
遗传学
肽序列
平滑肌
内分泌学
作者
Kang Li,Bin Li,Dihua Zhang,Tailai Du,Huanjiao Jenny Zhou,Gang Dai,Youchen Yan,Nailin Gao,Xiaodong Zhuang,Xinxue Liao,Chen Liu,Yugang Dong,Demeng Chen,Liang‐Hu Qu,Jing‐Song Ou,Jianhua Yang,Zhan‐Peng Huang
出处
期刊:Cardiovascular Research
[Oxford University Press]
日期:2023-03-21
卷期号:119 (8): 1763-1779
被引量:1
摘要
Abstract Aims The plasticity of vascular smooth muscle cells (VSMCs) enables them to alter phenotypes under various physiological and pathological stimuli. The alteration of VSMC phenotype is a key step in vascular diseases, including atherosclerosis. Although the transcriptome shift during VSMC phenotype alteration has been intensively investigated, uncovering multiple key regulatory signalling pathways, the translatome dynamics in this cellular process, remain largely unknown. Here, we explored the genome-wide regulation at the translational level of human VSMCs during phenotype alteration. Methods and results We generated nucleotide-resolution translatome and transcriptome data from human VSMCs undergoing phenotype alteration. Deep sequencing of ribosome-protected fragments (Ribo-seq) revealed alterations in protein synthesis independent of changes in messenger ribonucleicacid levels. Increased translational efficiency of many translational machinery components, including ribosomal proteins, eukaryotic translation elongation factors and initiation factors were observed during the phenotype alteration of VSMCs. In addition, hundreds of candidates for short open reading frame-encoded polypeptides (SEPs), a class of peptides containing 200 amino acids or less, were identified in a combined analysis of translatome and transcriptome data with a high positive rate in validating their coding capability. Three evolutionarily conserved SEPs were further detected endogenously by customized antibodies and suggested to participate in the pathogenesis of atherosclerosis by analysing the transcriptome and single cell RNA-seq data from patient atherosclerotic artery samples. Gain- and loss-of-function studies in human VSMCs and genetically engineered mice showed that these SEPs modulate the alteration of VSMC phenotype through different signalling pathways, including the mitogen-activated protein kinase pathway and p53 pathway. Conclusion Our study indicates that an increase in the capacity of translation, which is attributable to an increased quantity of translational machinery components, mainly controls alterations of VSMC phenotype at the level of translational regulation. In addition, SEPs could function as important regulators in the phenotype alteration of human VSMCs.
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