@article{fae6ba2a8d5047aa8694d9284af4c919,
title = "H/ACA snRNP–dependent ribosome biogenesis regulates translation of polyglutamine proteins",
abstract = "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.",
author = "Breznak, {Shane M.} and Yingshi Peng and Limin Deng and Kotb, {Noor M.} and Zachary Flamholz and Rapisarda, {Ian T.} and Martin, {Elliot T.} and LaBarge, {Kara A.} and Dan Fabris and Gavis, {Elizabeth R.} and Prashanth Rangan",
note = "Funding Information: We are grateful to all members of the Rangan laboratory, F. Marlow, D. Siekhaus, and Life Science Editors for discussion and comments on the manuscript. We would like to thank the Lehmann laboratory for the Egl antibody, A. Teleman for the p-S6 antibody, and Bloomington Drosophila Stock Center, Vienna Drosophila Resource Center, and FlyBase for fly stocks, reagents, and databases. Furthermore, we would like to thank the CFG Facility at the University at Albany (UAlbany) for performing RNA-seq analyses. We would also like to thank A. Biswas (Princeton University) for helping with bioinformatics support. P.R. was funded by NIH/NIGMS RO1GM11177 and NIH/NIGMS RO1GM135628. E.R.G. was funded by NIH/ NIGMS R35 GM126967. D.F. was funded by NIH/NIGMS R01 GM123050, NIH/NIGMS R01 GM121844, and NIH/NIGMS NIH/NIDA R01 DA04611. Publisher Copyright: {\textcopyright} 2023 American Association for the Advancement of Science. All rights reserved.",
year = "2023",
month = jun,
doi = "10.1126/sciadv.ade5492",
language = "English (US)",
volume = "9",
journal = "Science Advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "25",
}