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

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...

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Bibliographic Details
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
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work. Present address: Department of Cell Biology, Harvard Medical School, Boston, MA, USA. Present address: Medical Scientist Training Program, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
ISSN:	2375-2548 2375-2548
DOI:	10.1126/sciadv.ade5492