RNA-mediated gene regulation across generations

RNA-mediated gene regulation across generations

Studies using nematode worms, mice, and humans suggest that diet and stress can influence descendants’ metabolism and longevity. Genetic evidence indicates that double-stranded (ds) RNA molecules ingested by worms can silence sequence-matched genes in offspring through epigenetic mechanisms.

By injecting fluorescent dsRNA into Caenorhabditis elegans worms and by feeding dsRNA-producing bacteria to the worms, researchers. found that extracellular dsRNA in parent worms was transported along with yolk to oocytes, where the molecules accumulated in concentrated clumps.

Once transferred from oocytes to embryos, dsRNA spread between cells during embryonic development and silenced matching genes. Vertical transfer of dsRNA and cross-generational gene silencing occurred regardless of whether the target gene was present in the parent with extracellular dsRNA.

Further, a receptor on the surface of oocytes called RME-2, which helps internalize yolk into oocytes, served as a conduit for dsRNA in nematode worms. Further experiments suggested that dsRNA molecules that originate in the circulation of parent worms can enter offspring cells without direct exposure to the cytoplasm of oocytes.

According to the authors, the findings point to the tantalizing but unproven possibility that extracellular RNA molecules might serve as a vehicle for the transfer of experience-dependent gene regulatory information across generations.