Pseudouridine-dependent ribosome biogenesis regulates translation of polyglutamine proteins during Drosophila oogenesis

Abstract

Stem cells in many systems, including Drosophila germline stem cells (GSCs), increase ribosome biogenesis and translation during terminal differentiation. Here, we show that pseudouridylation of ribosomal RNA (rRNA) mediated by the H/ACA box is required for ribosome biogenesis and oocyte specification. Reducing ribosome levels during differentiation decreased the translation of a subset of mRNAs that are enriched for CAG 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 TOR activity to elevate ribosome levels in H/ACA box-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.