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Biomolecules 2018, 8(3), 54;

A Novel Class of tRNA-Derived Small Non-Coding RNAs Respond to Myocardial Hypertrophy and Contribute to Intergenerational Inheritance

College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China
College of Life and Science, Sichuan Agricultural University, Chengdu 611130, China
Chongqing Academy of Animal Sciences, Chongqing 402460, China
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Received: 14 April 2018 / Revised: 12 June 2018 / Accepted: 9 July 2018 / Published: 16 July 2018
(This article belongs to the Special Issue Biomolecules for Translational Approaches in Cardiology)
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tRNA-derived fragments (tRFs) are a new class of non-coding RNA that play an important role in regulating cellular RNA processing and protein translation. However, there is currently no study reporting the influence of tRFs on myocardial hypertrophy. In this study, we used an isoproterenol (ISO)-induced myocardial hypertrophy rat model. Small RNA (<40 nts) transcriptome sequencing was used to select differentially expressed tRFs. We also compared the tRFs expression pattern in F0 sperm and the hearts of F1 offspring between the myocardial hypertrophy group (Hyp) and the control group (Con). Isoproterenol successfully induced a typical cardiac hypertrophy model in our study. Small RNA-seq revealed that tRFs were extremely enriched (84%) in the Hyp heart. Overexpression of tRFs1 and tRFs2 both enlarged the surface area of cardiac cells and increased expression of hypertrophic markers (ANF, BNP, and β-MHC). Luciferase reporter assay identified that tRFs1 directly target 3′UTR of Timp3. tRFs1, tRFs2, tRFs3, and tRFs4 were also highly expressed in Hyp F0 sperm and in Hyp F1 offspring hearts, but there was no differential expression of tRFs7, tRFs9, and tRFs10. Compared to Con F1 offspring, Hyp F1 offspring had elevated expression levels of β-MHC and ANP genes, and they had increased fibrosis and apoptosis in their hearts. These results demonstrated that tRFs are involved in regulating the response of myocardial hypertrophy. Besides, tRFs might serve as novel epigenetic factors that contribute to the intergenerational inheritance of cardiac hypertrophy. View Full-Text
Keywords: tRNA fragments; myocardial hypertrophy; intergenerational inheritance tRNA fragments; myocardial hypertrophy; intergenerational inheritance

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Shen, L.; Gan, M.; Tan, Z.; Jiang, D.; Jiang, Y.; Li, M.; Wang, J.; Li, X.; Zhang, S.; Zhu, L. A Novel Class of tRNA-Derived Small Non-Coding RNAs Respond to Myocardial Hypertrophy and Contribute to Intergenerational Inheritance. Biomolecules 2018, 8, 54.

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