Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs

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 ZhengRebekah Woolsey, David Quilici, Qiwei Zhai, Lei Li, Tong Zhou, Wei Yan, Frank Lyko, Ying Zhang, Qi Zhou, Enkui Duan, Qi Chen

Research output: Contribution to journalArticle

47 Citations (Scopus)

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 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 (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.

Original languageEnglish (US)
Pages (from-to)535-540
Number of pages6
JournalNature Cell Biology
Volume20
Issue number5
DOIs
StatePublished - May 1 2018
Externally publishedYes

Fingerprint

Small Untranslated RNA
Spermatozoa
RNA
High Fat Diet
tRNA Methyltransferases
Untranslated RNA
Transfer RNA
Epigenomics
Phenotype
Messenger RNA

ASJC Scopus subject areas

  • Cell Biology

Cite this

Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs. / Zhang, Yunfang; Zhang, Xudong; Shi, Junchao; Tuorto, Francesca; Li, Xin; Liu, Yusheng; Liebers, Reinhard; Zhang, Liwen; Qu, Yongcun; Qian, Jingjing; Pahima, Maya; Liu, Ying; Yan, Menghong; Cao, Zhonghong; Lei, Xiaohua; Cao, Yujing; Peng, Hongying; Liu, Shichao; Wang, Yue; Zheng, Huili; Woolsey, Rebekah; Quilici, David; Zhai, Qiwei; Li, Lei; Zhou, Tong; Yan, Wei; Lyko, Frank; Zhang, Ying; Zhou, Qi; Duan, Enkui; Chen, Qi.

In: Nature Cell Biology, Vol. 20, No. 5, 01.05.2018, p. 535-540.

Research output: Contribution to journalArticle

Zhang, Y, Zhang, X, Shi, J, Tuorto, F, Li, X, Liu, Y, Liebers, R, Zhang, L, Qu, Y, Qian, J, Pahima, M, Liu, Y, Yan, M, Cao, Z, Lei, X, Cao, Y, Peng, H, Liu, S, Wang, Y, Zheng, H, Woolsey, R, Quilici, D, Zhai, Q, Li, L, Zhou, T, Yan, W, Lyko, F, Zhang, Y, Zhou, Q, Duan, E & Chen, Q 2018, 'Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs', Nature Cell Biology, vol. 20, no. 5, pp. 535-540. https://doi.org/10.1038/s41556-018-0087-2
Zhang, Yunfang ; Zhang, Xudong ; Shi, Junchao ; Tuorto, Francesca ; Li, Xin ; Liu, Yusheng ; Liebers, Reinhard ; Zhang, Liwen ; Qu, Yongcun ; Qian, Jingjing ; Pahima, Maya ; Liu, Ying ; Yan, Menghong ; Cao, Zhonghong ; Lei, Xiaohua ; Cao, Yujing ; Peng, Hongying ; Liu, Shichao ; Wang, Yue ; Zheng, Huili ; Woolsey, Rebekah ; Quilici, David ; Zhai, Qiwei ; Li, Lei ; Zhou, Tong ; Yan, Wei ; Lyko, Frank ; Zhang, Ying ; Zhou, Qi ; Duan, Enkui ; Chen, Qi. / Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs. In: Nature Cell Biology. 2018 ; Vol. 20, No. 5. pp. 535-540.
@article{3409797731364a6fae2961515d1a51a4,
title = "Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs",
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 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 (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.",
author = "Yunfang Zhang and Xudong Zhang and Junchao Shi and Francesca Tuorto and Xin Li and Yusheng Liu and Reinhard Liebers and Liwen Zhang and Yongcun Qu and Jingjing Qian and Maya Pahima and Ying Liu and Menghong Yan and Zhonghong Cao and Xiaohua Lei and Yujing Cao and Hongying Peng and Shichao Liu and Yue Wang and Huili Zheng and Rebekah Woolsey and David Quilici and Qiwei Zhai and Lei Li and Tong Zhou and Wei Yan and Frank Lyko and Ying Zhang and Qi Zhou and Enkui Duan and Qi Chen",
year = "2018",
month = "5",
day = "1",
doi = "10.1038/s41556-018-0087-2",
language = "English (US)",
volume = "20",
pages = "535--540",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "5",

}

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

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 (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.

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 (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.

UR - http://www.scopus.com/inward/record.url?scp=85046007423&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85046007423&partnerID=8YFLogxK

U2 - 10.1038/s41556-018-0087-2

DO - 10.1038/s41556-018-0087-2

M3 - Article

C2 - 29695786

AN - SCOPUS:85046007423

VL - 20

SP - 535

EP - 540

JO - Nature Cell Biology

JF - Nature Cell Biology

SN - 1465-7392

IS - 5

ER -