Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Nature cell biology, 2018-05, Vol.20 (5), p.535

Ort / Verlag

England

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 . Increasing evidence now suggests that sperm small non-coding RNAs (sncRNAs) can mediate intergenerational transmission of paternally acquired phenotypes, including mental stress and metabolic disorders . 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 C, m 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 C contributes to the secondary structure and biological properties of sncRNAs, implicating sperm RNA modifications as an additional layer of paternal hereditary information.