(216) The X-linked Nuclear RNA Export Factor 2 (Nxf2) is Required for Mouse Spermatid Development

Ann Marie Lawson¹; Eden A. Dulka¹; Jacob L. Mueller¹

1. Department of Human Genetics, University of Michigan, Ann Arbor, USA

 

Abstract Text:

Nuclear RNA export factor 1 (Nxf1), an essential transporter of RNAs from the nucleus to the cytoplasm, has been independently duplicated as Nxf2 across eukaryotes. In worms, flies and mammals, Nxf2 is expressed predominantly in germ cells, but the germ cell function of mammalian Nxf2 remains unknown. Here, we discover X-linked Nxf2 is necessary for mouse male fertility on inbred genetic backgrounds due to defects in haploid spermatids. Specifically, Nxf2^∆/Y mice on C57BL/6J and SJL/J (≥N7 generations) genetic backgrounds lack mature sperm due to failure of spermatid elongation, and Nxf2^∆/Y mice on the 129S4/SvJaeJ (≥N4 generations) genetic background have reduced sperm counts and litter sizes. We discovered NXF2 interacts with nuclear pore and intercellular bridge proteins from immunoprecipitation-mass spectrometry in Nxf2^FLAG/Y mouse testes, consistent with a predicted role in RNA transport. Some NXF2 interactors were duplicated at the beginning of mammalian sex chromosome evolution, as with Nxf2, suggesting the co-evolution of a mammalian spermatid-specific complex important for RNA transport. Consistent with spermatid elongation defects in Nxf2^∆/Y mice, NXF2 localizes to spermatids at the early stages of elongation. Considering RNA transport and regulation are important features of haploid spermatid development and Nxf2 is a duplicate of a nuclear export gene, we hypothesize mouse Nxf2 has a role in spermatid-specific transport of RNAs.