CMMG Seminar Series - Co-Sponsored with Genomics@Wayne and CURES

Heidi Lempradl, PhD
Assistant Professor of Metabolic and Nutritional Programming, Center for Cancer and Cell Biology, Van Andel Institute

“piRNAs Mediate Intergenerational Inheritance of Metabolic State”

Abstract
Phenotypes induced by environmental factors can be inherited through the male germline without changing the DNA blueprint. Studies have implicated small RNAs in this intergenerational inheritance of paternal state. Here we elucidate the role of piRNAs and the piRNA pathway in intergenerational inheritance. We characterize the small RNA repertoire in the male Drosophila germline and provide evidence for the presence of an intact piRNA pathway and functional piRNAs in mature sperm. Using heterozygous piRNA pathway mutations we also show that piRNA levels in sperm correlate with expression levels in offspring embryos. Building on our previously established Drosophila model for InterGenerational Metabolic Reprogramming (IGMR) we present that an intact piRNA pathway is necessary for proper inheritance of paternal metabolic state. Taken together our findings uncover an essential role for the piRNA pathway in the inheritance of an environmentally induced paternal phenotype.