H/ACA snRNP-dependent ribosome biogenesis regulates translation of polyglutamine proteins

• Published in: Science advances Vol. 9; no. 25; p. eade5492
• Main Authors: Breznak, Shane M, Peng, Yingshi, Deng, Limin, Kotb, Noor M, Flamholz, Zachary, Rapisarda, Ian T, Martin, Elliot T, LaBarge, Kara A, Fabris, Dan, Gavis, Elizabeth R, Rangan, Prashanth
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 23-06-2023
• Subjects: Biomedicine and Life Sciences; Developmental Biology; Proteins - metabolism; Ribonucleoproteins, Small Nuclear - metabolism; Ribosomes - metabolism; RNA, Ribosomal; SciAdv r-articles; Sirolimus
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.ade5492

Stem cells in many systems, including
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.