Divergent functions of the RNA-binding protein, Mei-P26 in germline and somatic lineages of Drosophila testis.

The Drosophila TRIM-NHL family RNA-binding protein Mei-P26 has been implicated in suppressing tumorigenesis in the female germline. By restricting growth and proliferation while promoting differentiation within the ovarian stem cell lineage, Mei-P26 maintains germline homeostasis. Whether it plays comparable or distinct roles in the testis during spermatogenesis, however, remains unclear. Here we show that overexpression of mei-P26 in germline cells leads to truncated, agametic testes. These testes display germline cell cycle arrest and defective somatic cyst cell proliferation and differentiation, highlighting a failure in germline-soma coordination. By contrast, somatic overexpression of mei-P26 results in male-specific lethality. With the Gal80 ts system to circumvent this lethality, induction of mei-P26 in adult somatic cells promoted proliferation and differentiation of both germline and somatic cells, accompanied by upregulation of phospho-S6, indicating hyperactivation of the TOR signaling pathway. Our findings reveal that Mei-P26 exerts opposing, cell type-specific roles within the same tissue, restraining germline development while driving expansion of somatic cells. This study underscores the importance of cell-specific regulation by RNA-binding proteins and provides new insights into how misregulation of Mei-P26 may coordinate divergent cell fates within a shared tissue context-processes frequently disrupted in cancer, developmental disorders, and age-associated tissue decline.