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Title: Dnmt2 Mediates Intergenerational Transmission of Paternally Acquired Metabolic Disorders Through Sperm Small Non-Coding RNAs
Author: Yunfang Zhang, Xudong Zhang, Junchao Shi, Francesca Tuorto, Xin Li, Yusheng Liu, Reinhard Liebers, Liwen Zhang, Yongcun Qu, Jingjing Qian, Maya Pahima, Ying Liu, Menghong Yan, Zhonghong Cao, Xiaohua Lei, Yujing Cao, Hongying Peng, Shichao Liu, Yue Wang, Huili Zheng, Rebekah Woolsey, David Quilici, Qiwei Zhai, Lei Li, Tong Zhou, Wei Yan, Frank Lyko, Ying Zhang, Qi Zhou, Enkui Duan, Qi Chen
Abstract: The discovery of RNAs (for example, messenger RNAs, non-coding RNAs) in sperm has opened the possibility that sperm may function by delivering additional paternal information aside from solely providing the DNA1. Increasing evidence now suggests that sperm small non-coding RNAs (sncRNAs) can mediate intergenerational transmission of paternally acquired phenotypes, including mental stress2,3 and metabolic disorders4,5,6. How sperm sncRNAs encode paternal information remains unclear, but the mechanism may involve RNA modifications. Here we show that deletion of a mouse tRNA methyltransferase, DNMT2, abolished sperm sncRNA-mediated transmission of high-fat-diet-induced metabolic disorders to offspring. Dnmt2 deletion prevented the elevation of RNA modifications (m5C, m2G) in sperm 30–40?nt RNA fractions that are induced by a high-fat diet. Also, Dnmt2 deletion altered the sperm small RNA expression profile, including levels of tRNA-derived small RNAs and rRNA-derived small RNAs, which might be essential in composing a sperm RNA ‘coding signature’ that is needed for paternal epigenetic memory. Finally, we show that Dnmt2-mediated m5C contributes to the secondary structure and biological properties of sncRNAs, implicating sperm RNA modifications as an additional layer of paternal hereditary information.
Corresponding author: Ying Zhang, Qi Zhou, Enkui Duan, Qi Chen
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PubYear: 2018
Volume: 20
Issue: 5
Page: 535-540
Journal: Nature Cell Biology
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URL: https://www.nature.com/articles/s41556-018-0087-2