Mouse Paternal RNAs Initiate a Pattern of Metabolic Disorders in a Line-Dependent Manner


Satir-Basaran G., Kianmehr L., Mehmetbeyoglu E., Korkmaz Bayram K., Memis M., Yilmaz Z., ...Daha Fazla

FRONTIERS IN GENETICS, cilt.13, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 13
  • Basım Tarihi: 2022
  • Doi Numarası: 10.3389/fgene.2022.839841
  • Dergi Adı: FRONTIERS IN GENETICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, EMBASE, Veterinary Science Database, Directory of Open Access Journals
  • Anahtar Kelimeler: sperm, diet, mouse, epigenetic, Dnmt2, non-coding RNAs, miRNAs, DNA, RNA hybrids, HIGH-FAT DIET, DNA METHYLTRANSFERASE, CYTOSINE METHYLATION, OBESITY, DNMT2, STABILITY, INHERITANCE, RIBOSOMES, TRAITS
  • Erciyes Üniversitesi Adresli: Evet

Özet

A wide range of diseases result from environmental effects, and the levels of many native transcripts are altered. The alteration of non-coding RNAs (ncRNAs) and transmission of the variation to the next generation is increasingly recognized as a marker of disease. However, the determining signals and mechanisms of RNA-induced heritability remain unclear. We performed functional tests with four different genotypes of mice maintained on a high-fat diet to trace the transfer of the obesity/diabetes phenotype to the next generation in order to detect common signals. Two founders of four mouse lines (B6/D2 hybrid and Dnmt2(-/-C57BL/6)) resist and do not change their phenotype while their sperm RNAs after microinjection into fertilized mouse eggs transfer the newly acquired phenotypes in a susceptible inbred line (C57BL/6 or Balb/c). Unexpectedly, in the same line of experiments, sperm RNA from animals raised on a normal diet when mixed with the sperm RNA from animals raised on a diet high in fat or synthetic miR-19b (inducer of obesity) affects or prevents the development of obesity and diabetes. However, it remains unclear what happens to ncRNA signaling under diet. With a comprehensive new analysis of the transcripts maintained as an RNA/DNA hybrid in sperm, we suggest that a fraction of the RNAs are stably attached to the genome. Thus, we propose that changes in the dynamics of ncRNA retention on DNA by factors such as transcriptional variations or lack of adequate methylation could serve as molecular markers to trace these epigenetics events.