| First Author | Zhang Y | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 6673 |
| PubMed ID | 34845238 | Mgi Jnum | J:315168 |
| Mgi Id | MGI:6830726 | Doi | 10.1038/s41467-021-26909-1 |
| Citation | Zhang Y, et al. (2021) Angiogenin mediates paternal inflammation-induced metabolic disorders in offspring through sperm tsRNAs. Nat Commun 12(1):6673 |
| abstractText | Paternal environmental inputs can influence various phenotypes in offspring, presenting tremendous implications for basic biology and public health and policy. However, which signals function as a nexus to transmit paternal environmental inputs to offspring remains unclear. Here we show that offspring of fathers with inflammation exhibit metabolic disorders including glucose intolerance and obesity. Deletion of a mouse tRNA RNase, Angiogenin (Ang), abolished paternal inflammation-induced metabolic disorders in offspring. Additionally, Ang deletion prevented the inflammation-induced alteration of 5'-tRNA-derived small RNAs (5'-tsRNAs) expression profile in sperm, which might be essential in composing a sperm RNA 'coding signature' that is needed for paternal epigenetic memory. Microinjection of sperm 30-40 nt RNA fractions (predominantly 5'-tsRNAs) from inflammatory Ang(+/+) males but not Ang(-/-) males resulted in metabolic disorders in the resultant offspring. Moreover, zygotic injection with synthetic 5'-tsRNAs which increased in inflammatory mouse sperm and decreased by Ang deletion partially resembled paternal inflammation-induced metabolic disorders in offspring. Together, our findings demonstrate that Ang-mediated biogenesis of 5'-tsRNAs in sperm contributes to paternal inflammation-induced metabolic disorders in offspring. |
