A translation control module coordinates germline stem cell differentiation with ribosome biogenesis during Drosophila oogenesis

Martin, Elliot T.; Blatt, Patrick; Nguyen, Elaine; Lahr, Roni M.; Selvam, Sangeetha; Yoon, Hyun Ah M; T, Pocchiari; Emtenani, Shamsi; Siekhaus, Daria E; Berman, Andrea J.; Fuchs, Gabriele; Rangan, Prashanth

doi:10.1016/j.devcel.2022.03.005

Cited by 20 publications

(16 citation statements)

References 106 publications

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“…To test if loss of the H/ACA box and consequent aberrant ribosome biogenesis affects mRNA translation during oogenesis, we performed polysome-seq of ovaries depleted of Nop60B in the germline and of gonads enriched for cysts stages (Flora et al, 2018; Martin et al, 2022; Ohlstein and McKearin, 1997). As enriching for early cyst stages includes a heat shock step (see methods), we also analyzed early-stage egg chambers to control for heat shock effects.…”

Section: Resultsmentioning

confidence: 99%

“…Defects in ribosome biogenesis can impair stem cell differentiation and lead to diseases collectively called ribosomopathies (Armistead and Triggs-Raine, 2014; Barlow et al, 2010; Brooks et al, 2014; Calo et al, 2018; Higa-Nakamine et al, 2012; Mills and Green, 2017). Protein synthesis often increases during stem cell differentiation (Sanchez et al, 2016; Teixeira and Lehmann, 2019; Zhang et al, 2014), and inhibiting translation by modulating Target of Rapamycin (TOR) activity blocks terminal differentiation of various stem cells (Martin et al, 2022; Neumüller et al, 2008; Sanchez et al, 2016; Sun et al, 2010; Zhang et al, 2014). Nevertheless, how ribosome levels and translation control differentiation remains’ incompletely understood.…”

Section: Introductionmentioning

confidence: 99%

“…During Drosophila oogenesis, differentiation of germline stems cells (GSCs) to an oocyte is sensitive to both ribosome biogenesis and translation (Blatt et al, 2020; Cinalli et al, 2008; Martin et al, 2022; Sanchez et al, 2016; Zhang et al, 2014). Oogenesis occurs in ovarioles beginning with the germline stem cells (GSCs) in the germaria ( Figure 1A ) (Lehmann, 2012; Xie and Spradling, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Pseudouridine-dependent ribosome biogenesis regulates translation of polyglutamine proteins during Drosophila oogenesis

Breznak

Peng

Deng

et al. 2022

Preprint

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Stem cells in many systems, including Drosophila germline stem cells (GSCs), increase ribosome biogenesis and translation during terminal differentiation. Here, we show that pseudouridylation of ribosomal RNA (rRNA) mediated by the H/ACA box is required for ribosome biogenesis and oocyte specification. Reducing ribosome levels during differentiation decreased the translation of a subset of mRNAs that are enriched for CAG 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 TOR activity to elevate ribosome levels in H/ACA box-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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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pseudouridine-dependent ribosome biogenesis regulates translation of polyglutamine proteins during Drosophila oogenesis

Breznak

Peng

Deng

et al. 2022

Preprint

Self Cite

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“…Perhaps, similar mechanisms regulating 5’TOP mRNA translation during stress conditions are utilized during development. Recently, a role of the translational regulation of 5’TOP transcripts has been suggested in germline stem cell differentiation in Drosophila ( Martin et al, 2022 ) and in mouse adult neurogenesis ( Baser et al, 2019 ). It will be exciting to investigate if stress-associated pathways play a physiological role during the development of not only the cerebral cortex but also other tissues.…”

Section: Discussionmentioning

confidence: 99%

Integrated transcriptome and proteome analysis reveals posttranscriptional regulation of ribosomal genes in human brain organoids

Sidhaye

Trepte

Sepke

et al. 2023

eLife

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During development of the human cerebral cortex, multipotent neural progenitors generate excitatory neurons and glial cells. Investigations of the transcriptome and epigenome have revealed important gene regulatory networks underlying this crucial developmental event. However, the posttranscriptional control of gene expression and protein abundance during human corticogenesis remains poorly understood. We addressed this issue by using human telencephalic brain organoids grown using a dual reporter cell line to isolate neural progenitors and neurons and performed cell class and developmental stage-specific transcriptome and proteome analysis. Integrating the two datasets revealed modules of gene expression during human corticogenesis. Investigation of one such module uncovered mTOR-mediated regulation of translation of the 5’TOP element-enriched translation machinery in early progenitor cells. We show that in early progenitors partial inhibition of the translation of ribosomal genes prevents precocious translation of differentiation markers. Overall, our multiomics approach proposes novel posttranscriptional regulatory mechanisms crucial for the fidelity of cortical development.

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“…Perhaps, similar mechanisms regulating 5’TOP mRNA translation are utilized during development and during stress conditions. Recently, a role of the translational regulation of 5’TOP transcripts has been suggested in germline stem cell differentiation in Drosophila (Martin et al, 2022) and in mouse adult neurogenesis (Baser et al, 2019). It will be exciting to investigate if stress-associated pathways play a physiological role during the development of not only the cerebral cortex but also other tissues.…”

Section: Discussionmentioning

confidence: 99%

Integrated transcriptome and proteome analysis in human brain organoids reveals posttranscriptional regulation of ribosomal genes

Sidhaye

Trepte

Sepke

et al. 2022

Preprint

View full text Add to dashboard Cite

During development of the human cerebral cortex, multipotent neural progenitors generate excitatory neurons and glial cells. Investigations of the transcriptome and epigenome have revealed important gene regulatory networks underlying this crucial developmental event. However, the post-transcriptional control of gene expression and protein abundance during human corticogenesis remains poorly understood. We addressed this issue by using human telencephalic brain organoids grown using a dual reporter cell line to isolate neural progenitors and neurons and performed cell type and developmental stagespecific transcriptome and proteome analysis. Integrating the two datasets revealed modules of gene expression during human corticogenesis. Investigation of one such module uncovered mTOR-mediated translational regulation of the 5’TOP element-enriched translation machinery in early progenitor cells. We show that in early progenitors partial inhibition of the translation of ribosomal genes prevents precocious translation of differentiation markers. Overall, our multiomics approach reveals novel posttranscriptional regulatory mechanisms crucial for the fidelity of cortical development.HighlightsTranscriptome and proteome-based gene expression regulation during human corticogenesisDistinct posttranscriptional mechanisms for cell type-specific temporal gene expressionRibosomal mRNAs with 5’TOP motif are translated less efficiently in early progenitorsTranslational regulation of 5’TOP mRNAs ensures fidelity of cortical development

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A translation control module coordinates germline stem cell differentiation with ribosome biogenesis during Drosophila oogenesis

Cited by 20 publications

References 106 publications

Pseudouridine-dependent ribosome biogenesis regulates translation of polyglutamine proteins during Drosophila oogenesis

Pseudouridine-dependent ribosome biogenesis regulates translation of polyglutamine proteins during Drosophila oogenesis

Integrated transcriptome and proteome analysis reveals posttranscriptional regulation of ribosomal genes in human brain organoids

Integrated transcriptome and proteome analysis in human brain organoids reveals posttranscriptional regulation of ribosomal genes

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