FIGURE 8.

Proposed model: mechanism of GRTH regulation on miR-469 biogenesis that represses TP2 and Prm2 gene translation during spermatogenesis. GRTH plays a critical role to maintain homeostasis of a subset of mature miRNAs by regulating miRNA biogenesis via Drosha-DGCR8 microprocessor complex activation. Absence of GRTH up-regulates pri-miR-469 and Drosha-DGCR8 complex. pre-miR-469 transfers to cytoplasmic sites where it is further processed via Dicer-dependent pathways to generate mature miR-469. miRNA-469 silences TP2 and Prm2 by its association at the coding region through RNA-induced silencing complex. This regulation ultimately controls the temporal progression of spermatogenesis via miR-469 inhibitory action on TP2/Prm2 protein expression, which is essential for their timely expression leading to its chromatin compactation in spermatids and the progress of spermatogenesis.