Mammalian Tudor-Related Genes in the Male Germline.

Abstract

Germ cells of many animals possess characteristic cytoplasmic structures termed germinal granules or nuage. Germinal granules are ribonucleoprotein (RNP) rich amorphous aggregates lacking limiting membranes, and their molecular composition is evolutionarily conserved in divergent species. Studies on germinal granules in several model animals, such as Drosophila and C. elegans, have mainly focused on the asymmetric partitioning of these RNP structures to prospective germ cells during early embryogenesis. In mammals, on the other hand, germinal granules become discernible at later stages of germ cell differentiation, i.e. in spermatogenesis and oogenesis. We previously showed that tudor domain containing (Tdrd) genes, including Tdrd1, 6, 7, and 9, encode a conserved class of germinal granule proteins in mammals. These germline tudor members are all essential for male fertility in mice, with each having a distinct and non-redundant role at different stages of spermatogenesis. Further, recent genetic and biochemical studies by our group and others indicate their key functions in the assembly and regulation of mammalian germinal granules, including the close association of inter-mitochondrial cement with the piwi-small RNA pathway and the dynamic RNP remodeling of chromatoid bodies, which incorporate both germline and ubiquitous features as spermatogenesis proceeds. (platform)