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

H/ACA snRNP依赖的核糖体生物合成调控多聚谷氨酰胺蛋白的翻译

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作者:Shane M Breznak ,Yingshi Peng ,Limin Deng ,Noor M Kotb ,Zachary Flamholz ,Ian T Rapisarda ,Elliot T Martin ,Kara A LaBarge ,Dan Fabris ,Elizabeth R Gavis ,Prashanth Rangan

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.

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