Translatome and Transcriptome Profiling of Hypoxic-Induced Rat Cardiomyocytes.

Translatome and Transcriptome Profiling of Hypoxic-Induced Rat Cardiomyocytes.
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缺氧诱导的大鼠心肌细胞的翻译组和转录组分析

DOI:
10.1016/j.omtn.2020.10.019
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发表时间:
2020-12-04
期刊:
Molecular therapy. Nucleic acids
影响因子:
--
通讯作者:
Zhang Z
Zhang Z
中科院分区:
其他
文献类型:
--
作者:
Shen Z;Zeng L;Zhang Z

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成人心脏缺氧作为重要的发病机制,可对心脏损伤和功能障碍产生不利影响。反映细胞对缺氧反应的整体转录组和翻译组尚未在心肌中得到广泛研究。在这项研究中,我们对体内外不同时期缺氧应激的大鼠心脏组织和 H9C2 细胞进行了 RNA 测序 (RNA-seq) 和核糖体分析技术 (polyribo-seq)。时间基因表达谱显示转录组和翻译组的区别,主要集中在细胞凋亡、自噬、DNA修复、血管生成、血管过程以及心肌细胞增殖和分化。 GNAI3、SEPT4、FANCL、BNIP3、TBX3、ESR2、PTGS2、KLF4和ADRB2等大量转录水平和翻译水平密切相关的基因被鉴定在5'UTR中拥有共同的RNA基序“5'-GAAGCUGCC-3'”。 NCBP3 被进一步确定可识别该 RNA 基序并促进缺氧应激下心肌中的翻译过程。综上所述,我们的数据显示了缺氧暴露后转录组和翻译组变化之间的密切联系,强调了翻译调控在相关研究中的重要性。当前研究中描述的分子反应可能是深入了解缺氧对心脏病影响的机制的宝贵资源。沉等人。通过 RNA-seq 和体内外多核糖体分析来表征缺氧诱导的心肌细胞中翻译组和转录组的景观。基因 5'UTR 中的 RNA 基序和 NCBP3 与 RNA 丰度具有良好的相关性,已被鉴定用于响应缺氧的翻译促进。
Adult cardiac hypoxia as a crucial pathogenesis factor can induce detrimental effects on cardiac injury and dysfunction. The global transcriptome and translatome reflecting the cellular response to hypoxia have not yet been extensively studied in myocardium. In this study, we conducted RNA sequencing (RNA-seq) and ribosome profiling technique (polyribo-seq) in rat heart tissues and H9C2 cells exposed to different periods of hypoxia stress in vivo and in vitro. The temporal gene-expression profiling displayed the distinction of transcriptome and translatome, which were mainly concentrated in cell apoptosis, autophagy, DNA repair, angiogenesis, vascular process, and cardiac cell proliferation and differentiation. A large number of genes such as GNAI3, SEPT4, FANCL, BNIP3, TBX3, ESR2, PTGS2, KLF4, and ADRB2, whose transcript and translation levels are closely correlated, were identified to own a common RNA motif “5′-GAAGCUGCC-3′” in 5′ UTR. NCBP3 was further determined to recognize this RNA motif and facilitate translational process in myocardium under hypoxia stress. Taken together, our data show the close connection between alterations of transcriptome and translatome after hypoxia exposure, emphasizing the significance of translational regulation in related studies. The profiled molecular responses in current study may be valuable resources for advanced understanding of the mechanisms underlying hypoxia-induced effect on heart diseases. Shen et al. characterize a landscape of translatome and transcriptome in hypoxia-induced cardiomyocytes by RNA-seq and polysome profiling in vivo and in vitro. RNA motif and NCBP3 in 5′ UTR of genes with a good correlation of RNA abundance are identified for translational facilitation responding to hypoxia.
RNA-Seq 鉴定了心力衰竭的新心肌基因表达特征。
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