|
| Status |
Public on Mar 06, 2018 |
| Title |
Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs |
| Organism |
Mus musculus |
| Experiment type |
Non-coding RNA profiling by high throughput sequencing
Expression profiling by high throughput sequencing
|
| Summary |
The discovery of RNAs (e.g. mRNAs, non-coding RNAs) in sperm has opened the possibility that sperm may function in delivering additional paternal information aside from solely providing the DNA1. 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 (HFD)-induced metabolic disorders to offspring. Dnmt2 deletion prevented the elevation of RNA modifications (m5C, m2G) in sperm 30-40nt RNA fractions that are induced by HFD. Also, Dnmt2 deletion altered the sperm small RNA expression profile, including levels of tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNA-28S), 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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| Overall design |
Mature sperm small RNA profiles among Dnmt2 (Trdmt1)+/+ High-fat-diet (HFD), Dnmt2+/+ Normal-diet (ND), Dnmt2-/- HFD and Dnmt2-/- ND mouse; Transfection of synthesized tsRNAs (with site-specific m5C modifications) into 3T3 cell line.
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| |
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| Contributor(s) |
Shi J, Chen Q |
| Citation(s) |
29695786 |
| |
| Submission date |
Apr 11, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Junchao Shi |
| E-mail(s) |
shijc1990@gmail.com
|
| Organization name |
University of California, Riverside
|
| Department |
Division of Biomedical Sciences, School of Medicine
|
| Street address |
900 University Ave
|
| City |
Riverside |
| State/province |
CA |
| ZIP/Postal code |
92521 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
|
| Samples (16)
|
| GSM2574271 |
Dnmt2-/- high fat diet sperm rep1 |
| GSM2805957 |
3T3 cells with empty transfection rep1 |
| GSM2805958 |
3T3 cells with empty transfection rep2 |
| GSM2805959 |
3T3 cells with 3'tsRNA-Gly (no m5C) transfection rep1 |
| GSM2805960 |
3T3 cells with 3'tsRNA-Gly (no m5C) transfection rep2 |
| GSM2805961 |
3T3 cells with 3'tsRNA-Gly (4 x m5C) transfection rep1 |
| GSM2805962 |
3T3 cells with 3'tsRNA-Gly (4 x m5C) transfection rep2 |
| GSM2805963 |
3T3 cells with 3'tsRNA-Gly (5 x m5C) transfection rep1 |
| GSM2805964 |
3T3 cells with 3'tsRNA-Gly (5 x m5C) transfection rep2 |
| GSM2938764 |
Dnmt2+/+ normal diet sperm rep2 |
| GSM2938765 |
Dnmt2+/+ high fat diet sperm rep2 |
| GSM2938766 |
Dnmt2-/- normal diet sperm rep2 |
| GSM2938767 |
Dnmt2-/- high fat diet sperm rep2 |
|
| Relations |
| BioProject |
PRJNA382549 |
| SRA |
SRP103802 |
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