Breznak, S.M., Peng, Y., Deng, L., Kotb, N.M., Flamholz, Z., Rapisarda, I.T., Martin, E.T., LaBarge, K.A., Fabris, D., Gavis, E.R., Rangan, P. (2023). H/ACA snRNP-dependent ribosome biogenesis regulates translation of polyglutamine proteins.  Sci. Adv. 9(25): eade5492.

FBrf0256853

Research paper

Stem cells in many systems, including Drosophila germline stem cells (GSCs), increase ribosome biogenesis and translation during terminal differentiation. Here, we show that the H/ACA small nuclear ribonucleoprotein (snRNP) complex that promotes pseudouridylation of ribosomal RNA (rRNA) and ribosome biogenesis is required for oocyte specification. Reducing ribosome levels during differentiation decreased the translation of a subset of messenger RNAs that are enriched for CAG trinucleotide repeats and encode polyglutamine-containing proteins, including differentiation factors such as RNA-binding Fox protein 1. Moreover, ribosomes were enriched at CAG repeats within transcripts during oogenesis. Increasing target of rapamycin (TOR) activity to elevate ribosome levels in H/ACA snRNP complex-depleted germlines suppressed the GSC differentiation defects, whereas germlines treated with the TOR inhibitor rapamycin had reduced levels of polyglutamine-containing proteins. Thus, ribosome biogenesis and ribosome levels can control stem cell differentiation via selective translation of CAG repeat-containing transcripts.

PMC10284551 (PMC) (EuropePMC)