Simultaneous activation of Tor and suppression of ribosome biogenesis by TRIM-NHL proteins promotes terminal differentiation
Summary: Tissue development and homeostasis depend on the balance between growth and terminal differentiation, but the mechanisms coordinating these processes remain elusive. Accumulating evidence indicates that ribosome biogenesis (RiBi) and protein synthesis, two cellular processes sustaining grow...
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Language: | English |
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Elsevier
2023-03-01
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Series: | Cell Reports |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723001924 |
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author | Jinghua Gui Tamsin J. Samuels Katarina Z.A. Grobicki Felipe Karam Teixeira |
author_facet | Jinghua Gui Tamsin J. Samuels Katarina Z.A. Grobicki Felipe Karam Teixeira |
author_sort | Jinghua Gui |
collection | DOAJ |
description | Summary: Tissue development and homeostasis depend on the balance between growth and terminal differentiation, but the mechanisms coordinating these processes remain elusive. Accumulating evidence indicates that ribosome biogenesis (RiBi) and protein synthesis, two cellular processes sustaining growth, are tightly regulated and yet can be uncoupled during stem cell differentiation. Using the Drosophila adult female germline stem cell and larval neuroblast systems, we show that Mei-P26 and Brat, two Drosophila TRIM-NHL paralogs, are responsible for uncoupling RiBi and protein synthesis during differentiation. In differentiating cells, Mei-P26 and Brat activate the target of rapamycin (Tor) kinase to promote translation, while concomitantly repressing RiBi. Depletion of Mei-P26 or Brat results in defective terminal differentiation, which can be rescued by ectopic activation of Tor together with suppression of RiBi. Our results indicate that uncoupling RiBi and translation activities by TRIM-NHL activity creates the conditions required for terminal differentiation. |
first_indexed | 2024-04-10T05:49:41Z |
format | Article |
id | doaj.art-5ccec6993c924cd6939eac3170b65e7c |
institution | Directory Open Access Journal |
issn | 2211-1247 |
language | English |
last_indexed | 2024-04-10T05:49:41Z |
publishDate | 2023-03-01 |
publisher | Elsevier |
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series | Cell Reports |
spelling | doaj.art-5ccec6993c924cd6939eac3170b65e7c2023-03-05T04:24:18ZengElsevierCell Reports2211-12472023-03-01423112181Simultaneous activation of Tor and suppression of ribosome biogenesis by TRIM-NHL proteins promotes terminal differentiationJinghua Gui0Tamsin J. Samuels1Katarina Z.A. Grobicki2Felipe Karam Teixeira3Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UKDepartment of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UKDepartment of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UKDepartment of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK; Corresponding authorSummary: Tissue development and homeostasis depend on the balance between growth and terminal differentiation, but the mechanisms coordinating these processes remain elusive. Accumulating evidence indicates that ribosome biogenesis (RiBi) and protein synthesis, two cellular processes sustaining growth, are tightly regulated and yet can be uncoupled during stem cell differentiation. Using the Drosophila adult female germline stem cell and larval neuroblast systems, we show that Mei-P26 and Brat, two Drosophila TRIM-NHL paralogs, are responsible for uncoupling RiBi and protein synthesis during differentiation. In differentiating cells, Mei-P26 and Brat activate the target of rapamycin (Tor) kinase to promote translation, while concomitantly repressing RiBi. Depletion of Mei-P26 or Brat results in defective terminal differentiation, which can be rescued by ectopic activation of Tor together with suppression of RiBi. Our results indicate that uncoupling RiBi and translation activities by TRIM-NHL activity creates the conditions required for terminal differentiation.http://www.sciencedirect.com/science/article/pii/S2211124723001924CP: Developmental biology |
spellingShingle | Jinghua Gui Tamsin J. Samuels Katarina Z.A. Grobicki Felipe Karam Teixeira Simultaneous activation of Tor and suppression of ribosome biogenesis by TRIM-NHL proteins promotes terminal differentiation Cell Reports CP: Developmental biology |
title | Simultaneous activation of Tor and suppression of ribosome biogenesis by TRIM-NHL proteins promotes terminal differentiation |
title_full | Simultaneous activation of Tor and suppression of ribosome biogenesis by TRIM-NHL proteins promotes terminal differentiation |
title_fullStr | Simultaneous activation of Tor and suppression of ribosome biogenesis by TRIM-NHL proteins promotes terminal differentiation |
title_full_unstemmed | Simultaneous activation of Tor and suppression of ribosome biogenesis by TRIM-NHL proteins promotes terminal differentiation |
title_short | Simultaneous activation of Tor and suppression of ribosome biogenesis by TRIM-NHL proteins promotes terminal differentiation |
title_sort | simultaneous activation of tor and suppression of ribosome biogenesis by trim nhl proteins promotes terminal differentiation |
topic | CP: Developmental biology |
url | http://www.sciencedirect.com/science/article/pii/S2211124723001924 |
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