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

被引：5

作者：

Breznak, Shane M. ^{[1
]}

Peng, Yingshi ^{[2
,7
]}

Deng, Limin ^{[1
,3
]}

Kotb, Noor M. ^{[1
,4
]}

Flamholz, Zachary ^{[2
,8
]}

Rapisarda, Ian T. ^{[1
,5
]}

Martin, Elliot T. ^{[1
]}

LaBarge, Kara A. ^{[1
]}

Fabris, Dan ^{[1
,3
]}

Gavis, Elizabeth R. ^{[2
]}

Rangan, Prashanth ^{[1
,6
]}

机构：

[1] SUNY Albany, RNA Inst, Dept Biol Sci, 1400 Washington Ave, LSRB 2033D, Albany, NY 12222 USA

[2] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA

[3] Univ Connecticut, Dept Chem, 55N Eagleville Rd, Storrs, CT 06269 USA

[4] SUNY Albany, Dept Biomed Sci, Sch Publ Hlth, Albany, NY 12144 USA

[5] Lake Erie Coll Osteopath Med, Coll Med, 1858 W Grandview Blvd, Erie, PA 16509 USA

[6] Icahn Sch Med Mt Sinai, Black Family Stem Cell Inst, Dept Cell Dev & Regenerat Biol, 1 Gustave L Levy Pl, New York, NY 10029 USA

[7] Harvard Med Sch, Dept Cell Biol, Boston, MA USA

[8] Albert Einstein Coll Med, Med Scientist Training Program, Bronx, NY 10461 USA

来源：

SCIENCE ADVANCES | 2023年 / 9卷 / 25期

关键词：

GERMLINE STEM-CELL; GENE-REGULATION; DROSOPHILA; EXPRESSION; EGALITARIAN; TOXICITY; DEFECTS; COMPLEX; CYST;

D O I：

10.1126/sciadv.ade5492

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：14

共 60 条

[1] Proteins Containing Expanded Polyglutamine Tracts and Neurodegenerative Disease[J]. Adegbuyiro, Adewale;Sedighi, Faezeh;Pilkington, Albert W.;Groover, Sharon;Legleiter, Justin. BIOCHEMISTRY, 2017(09)
[2] Diverse diseases from a ubiquitous process: The ribosomopathy paradox[J]. Armistead, Joy;Triggs-Raine, Barbara. FEBS LETTERS, 2014(09)
[3] New insights into 5q-syndrome as a ribosomopathy[J]. Barlow, Jillian L.;Drynan, Lesley F.;Trim, Nicola L.;Erber, Wendy N.;Warren, Alan J.;McKenzie, Andrew N. J. CELL CYCLE, 2010(21)
[4] Post-transcriptional gene regulation regulates germline stem cell to oocyte transition during Drosophila oogenesis[J]. Blatt, Patrick;Martin, Elliot T.;Breznak, Shane M.;Rangan, Prashanth. MATERNAL EFFECT GENES IN DEVELOPMENT, 2020
[5] A Novel Ribosomopathy Caused by Dysfunction of RPL10 Disrupts Neurodevelopment and Causes X-Linked Microcephaly in Humans[J]. Brooks, Susan S.;Wall, Alissa L.;Golzio, Christelle;Reid, David W.;Kondyles, Amalia;Willer, Jason R.;Botti, Christina;Nicchitta, Christopher V.;Katsanis, Nicholas;Davis, Erica E. GENETICS, 2014(02)
[6] CARPENTER ATC, 1994, CIBA F SYMP, V182, P223
[7] Repression of Pumilio Protein Expression by Rbfox1 Promotes Germ Cell Differentiation[J]. Carreira-Rosario, Arnaldo;Bhargava, Varsha;Hillebrand, Jens;Kollipara, Rahul K.;Ramaswami, Mani;Buszczakl, Michael. DEVELOPMENTAL CELL, 2016(05)
[8] Dpp signaling silences bam transcription directly to establish asymmetric divisions of germline stem cells[J]. Chen, DH;McKearin, D. CURRENT BIOLOGY, 2003(20)
[9] A discrete transcriptional silencer in the bam gene determines asymmetric division of the Drosophila germline stem cell[J]. Chen, DH;McKearin, DM. DEVELOPMENT, 2003(06)
[10] Development of a tissue-specific ribosome profiling approach in Drosophila enables genome-wide evaluation of translational adaptations[J]. Chen, Xun;Dickman, Dion. PLOS GENETICS, 2017(12)

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