Uncoupling of ribosome biogenesis and Tor activation by TRIM-NHL proteins promotes terminal differentiation

Proper stem cell differentiation relies on a balance between cellular growth and terminal differentiation, but the mechanisms coordinating these processes remain elusive. Recent studies indicate that ribosome biogenesis (RiBi) and protein synthesis, two of the most energy-consuming cellular processes supporting growth, are tightly regulated and yet can be uncoupled during stem cell fate transitions[1][1]–[6][2]. Here, using the Drosophila adult female germline stem cell (GSC) and larval neuroblast (NB) systems, we show that Mei-P26 and Brat[7][3], two Drosophila TRIM-NHL paralogues of the mammalian TRIM32 protein family, are responsible for uncoupling RiBi and protein synthesis during GSC and NB differentiation, respectively. This is achieved by TRIM-NHL-mediated activation of the Target of rapamycin (Tor) kinase and concomitant repression of RiBi specifically during stem cell differentiation. In consequence, the anabolic reprogramming established by TRIM-NHL activity creates the conditions for terminal differentiation. In agreement with this, depletion of mei-P26 or brat , which results in excessive cellular growth and defective terminal differentiation[8][4]–[10][5], can be counterbalanced by ectopic activation of Tor together with suppression of RiBi, allowing completion of differentiation. Our work indicates that TRIM-NHL proteins uncouple RiBi and translation activities to coordinate growth and differentiation, and proposes that the control of cellular resources provides a meter for terminal differentiation. ### Competing Interest Statement The authors have declared no competing interest. [1]: #ref-1 [2]: #ref-6 [3]: #ref-7 [4]: #ref-8 [5]: #ref-10