TY - JOUR
T1 - Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs
AU - Zhang, Yunfang
AU - Zhang, Xudong
AU - Shi, Junchao
AU - Tuorto, Francesca
AU - Li, Xin
AU - Liu, Yusheng
AU - Liebers, Reinhard
AU - Zhang, Liwen
AU - Qu, Yongcun
AU - Qian, Jingjing
AU - Pahima, Maya
AU - Liu, Ying
AU - Yan, Menghong
AU - Cao, Zhonghong
AU - Lei, Xiaohua
AU - Cao, Yujing
AU - Peng, Hongying
AU - Liu, Shichao
AU - Wang, Yue
AU - Zheng, Huili
AU - Woolsey, Rebekah
AU - Quilici, David
AU - Zhai, Qiwei
AU - Li, Lei
AU - Zhou, Tong
AU - Yan, Wei
AU - Lyko, Frank
AU - Zhang, Ying
AU - Zhou, Qi
AU - Duan, Enkui
AU - Chen, Qi
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/5/1
Y1 - 2018/5/1
N2 - 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 DNA 1 . Increasing evidence now suggests that sperm small non-coding RNAs (sncRNAs) can mediate intergenerational transmission of paternally acquired phenotypes, including mental stress 2,3 and metabolic disorders 4-6 . 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 (m 5 C, m 2 G) 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 m 5 C contributes to the secondary structure and biological properties of sncRNAs, implicating sperm RNA modifications as an additional layer of paternal hereditary information.
AB - 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 DNA 1 . Increasing evidence now suggests that sperm small non-coding RNAs (sncRNAs) can mediate intergenerational transmission of paternally acquired phenotypes, including mental stress 2,3 and metabolic disorders 4-6 . 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 (m 5 C, m 2 G) 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 m 5 C contributes to the secondary structure and biological properties of sncRNAs, implicating sperm RNA modifications as an additional layer of paternal hereditary information.
UR - https://www.scopus.com/pages/publications/85046007423
UR - https://www.scopus.com/pages/publications/85046007423#tab=citedBy
U2 - 10.1038/s41556-018-0087-2
DO - 10.1038/s41556-018-0087-2
M3 - Article
C2 - 29695786
AN - SCOPUS:85046007423
SN - 1465-7392
VL - 20
SP - 535
EP - 540
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 5
ER -