HEN1 is a regulator of piRNA metabolism, transcriptional regulation and mammalian male fertility

Within this project we will define the mechanism of action of HEN1 in mammals. HEN1 is an evolutionarily conserved protein with variant roles in species ranging from Arabidopsis, flies, and humans. Through the use of the first model of mammalian Hen1 dysfunction, we will define the biochemistry of this putative RNA methyltransferase in piRNA metabolism and in male fertility. We will identify critical HEN1-dependent targets, and make a preliminary assessment of the consequences of HEN1 dysfunction in a second mammal, the human. This project will define a mechanism of critical importance to mammalian male fertility and will have long-term relevance for the management of agricultural species and artificial reproductive technologies.