Translation ofTudor-SN, a novel terminal oligo-pyrimidine (TOP) mRNA, is regulated by the mTORC1 pathway in cardiomyocytes
Translation ofTudor-SN, a novel terminal oligo-pyrimidine (TOP) mRNA, is regulated by the mTORC1 pathway in cardiomyocytes
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Tudor-SN 是一种新型末端寡嘧啶 (TOP) mRNA，其翻译受心肌细胞中 mTORC1 通路的调节
DOI：
10.1080/15476286.2020.1827783
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发表时间：
2020-10-16
期刊：
影响因子：
4.1
通讯作者：
Yang, Jie
中科院分区：
文献类型：
--
作者：
Gan, Shihu;Su, Chao;Yang, Jie
在心脏发育过程中调控心肌细胞周期停滞的机制在很大程度上是未知的。我们以前已经发现Tudor葡萄球菌核酸酶(Tudor-SN)是一种细胞周期调节因子，并表明其表达水平与细胞增殖能力密切相关。在此，我们发现Tudor-SN在新生小鼠心肌中高表达，而在成年小鼠心肌中低表达。利用转录起始点数据库(DBTSS)，我们发现Tudor-SN是一个末端的寡嘧啶(TOP)mRNA。我们进一步证实，Tudor-SNmRNA的翻译效率受哺乳动物靶标雷帕霉素复合体1(MTORC1)途径的控制，这一结果在原代新生小鼠心肌细胞中被激活，在成年小鼠心肌细胞中被沉默；此外，这一结果在H9c2细胞中也得到了重复。我们还证明，成年心肌中Tudor-SN的下调是由于mTORC1途径的失活，以确保心脏的生长与身体其他部分的生长成比例。此外，我们还发现Tudor-SN参与了mTORC1介导的心肌细胞增殖的调节，进一步阐明了Tudor-SN与mTORC1通路的相关性。综上所述，我们的研究结果表明，Tudor-SN的翻译效率受心肌中mTORC1途径的调节，并且Tudor-SN参与了mTORC1介导的心肌细胞增殖和心脏发育的调节。
The mechanisms that regulate cell-cycle arrest of cardiomyocytes during heart development are largely unknown. We have previously identified Tudor staphylococcal nuclease (Tudor-SN) as a cell-cycle regulator and have shown that its expression level was closely related to cell-proliferation capacity. Herein, we found that Tudor-SN was highly expressed in neonatal mouse myocardia, but it was lowly expressed in that of adults. Using Data Base of Transcription Start Sites (DBTSS), we revealed thatTudor-SNwas a terminal oligo-pyrimidine (TOP) mRNA. We further confirmed that the translational efficiency ofTudor-SNmRNA was controlled by the mammalian target of rapamycin complex 1 (mTORC1) pathway, as revealed via inhibition of activated mTORC1 in primary neonatal mouse cardiomyocytes and activation of silenced mTORC1 in adult mouse myocardia; additionally, this result was recapitulated in H9c2 cells. We also demonstrated that the downregulation of Tudor-SN in adult myocardia was due to inactivation of the mTORC1 pathway to ensure that heart growth was in proportion to that of the rest of the body. Moreover, we revealed that Tudor-SN participated in the mTORC1-mediated regulation of cardiomyocytic proliferation, which further elucidated the correlation between Tudor-SN and the mTORC1 pathway. Taken together, our findings suggest that the translational efficiency of Tudor-SN is regulated by the mTORC1 pathway in myocardia and that Tudor-SN is involved in mTORC1-mediated regulation of cardiomyocytic proliferation and cardiac development.