Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs.
Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs.
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Dnmt2通过精子小非编码RNA介导父系获得性代谢紊乱的代际传播
DOI：
10.1038/s41556-018-0087-2
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发表时间：
2018-05
影响因子：
21.3
通讯作者：
Chen Q
中科院分区：
文献类型：
--
作者：
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
精子中RNA（例如信使RNA、非编码RNA）的发现开启了一种可能性，即精子除了单独提供DNA外，还可以通过传递额外的父系信息来发挥作用。越来越多的证据表明，精子小的非编码RNA（sncRNA）可以介导父系获得的表型的代际传递，包括精神压力和代谢紊乱。精子sncRNA如何编码父亲信息仍不清楚，但其机制可能涉及RNA修饰。在此，我们发现小鼠tRNA甲基转移酶DNMT 2的缺失可以阻止精子sncRNA介导的高脂饮食诱导的代谢紊乱向后代的传递，并阻止高脂饮食诱导的精子30-40 nt RNA片段中RNA修饰（m5 C，m2 G）的增加。此外，Dnmt 2缺失改变了精子小RNA的表达谱，包括tRNA衍生的小RNA和rRNA衍生的小RNA的水平，这可能是组成精子RNA“编码签名”所必需的，这是父亲的表观遗传记忆。最后，我们表明，Dnmt 2介导的m5 C有助于sncRNA的二级结构和生物学特性，暗示精子RNA修饰作为父系遗传信息的附加层。
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.Dnmt2deletion prevented the elevation of RNA modifications (m5C, m2G) in sperm 30–40 nt RNA fractions that are induced by a high-fat diet. Also,Dnmt2deletion 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.
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影响因子：
25
作者：
Gapp, Katharina;Jawaid, Ali;Sarkies, Peter;Bohacek, Johannes;Pelczar, Pawel;Prados, Julien;Farinelli, Laurent;Miska, Eric;Mansuy, Isabelle M.
通讯作者：
Mansuy, Isabelle M.
影响因子：
30.8
作者：
Ciabrelli F;Comoglio F;Fellous S;Bonev B;Ninova M;Szabo Q;Xuéreb A;Klopp C;Aravin A;Paro R;Bantignies F;Cavalli G
通讯作者：
Cavalli G
DOI：
10.1126/science.aaf7040
发表时间：
2016-07-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Holland ML;Lowe R;Caton PW;Gemma C;Carbajosa G;Danson AF;Carpenter AA;Loche E;Ozanne SE;Rakyan VK
通讯作者：
Rakyan VK
影响因子：
56.9
作者：
Goll, MG;Kirpekar, F;Bestor, TH
通讯作者：
Bestor, TH
影响因子：
56.9
作者：
Laprell, Friederike;Finkl, Katja;Mueller, Juerg
通讯作者：
Mueller, Juerg