The translational landscape of phenylephrine-treated neonatal rat cardiomyocytes [nsRNA-seq]

In this study, we generated nucleotide-resolution translatome as well as transcriptome data of isolated primary cardiomyocytes undergoing hypertrophy. More than 10,000 open reading frames (ORF) were detected from the deep sequencing of ribosome protected fragments orchestrating the shift of translatome in hypertrophied cardiomyocytes.We further identified more than 100 potential micropeptides encoded by uncharacterized small open reading frames (sORFs) in the long noncoding RNA genes. Over two-thirds of these micropeptide candidates were experimentally validated in a random test with three micropeptides showing regulatory function in cardiomyocyte hypertrophy via modulating the activities of Oxidative phosphorylation, Calcium signaling pathway, and MAPK signaling pathway.Our study provided a genome-wide overview of the translational controls of cardiomyocyte hypertrophy and demonstrated an unrecognized role of micropeptides in cardiomyocyte biology.本研究针对发生心肌肥大的分离原代心肌细胞，生成了核苷酸分辨率的翻译组（translatome）与转录组（transcriptome）数据。通过对核糖体保护片段（ribosome protected fragments）进行深度测序，本研究共检测到超过10000个开放阅读框（open reading frame, ORF），这些开放阅读框参与调控肥大心肌细胞中翻译组的表达转变。本研究进一步在长非编码RNA基因中，鉴定出超过100种由未注释小开放阅读框（small open reading frame, sORF）编码的潜在微肽（micropeptide）。在随机验证实验中，超过三分之二的候选微肽得到了实验验证；其中3种微肽可通过调控氧化磷酸化（oxidative phosphorylation）、钙信号通路（calcium signaling pathway）以及MAPK信号通路（MAPK signaling pathway）的活性，在心肌肥大过程中发挥调控功能。本研究从全基因组层面系统阐述了心肌肥大的翻译调控机制，并揭示了微肽在心肌细胞生物学中此前未被认知的重要作用。