Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs.
Nat Cell Biol
; 20(5): 535-540, 2018 05.
Article
in En
| MEDLINE
| ID: mdl-29695786
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 stress2,3 and metabolic disorders4-6. 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Spermatozoa
/
Glucose Metabolism Disorders
/
DNA (Cytosine-5-)-Methyltransferases
/
RNA, Small Untranslated
/
Paternal Inheritance
Type of study:
Diagnostic_studies
Limits:
Animals
Language:
En
Journal:
Nat Cell Biol
Year:
2018
Document type:
Article
Affiliation country:
China