Ribosome profiling reveals the role of yeast RNA-binding proteins Cth1 and Cth2 in translational regulation
Iron serves as a cofactor for enzymes involved in several steps of protein translation, but the control of translation during iron limitation is not understood at the molecular level. Here, we report a genome-wide analysis of protein translation in response to iron deficiency in yeast using ribosome profiling. We show that iron depletion affects global protein synthesis and leads to translational repression of multiple genes involved in iron-related processes. Furthermore, we demonstrate that the RNA-binding proteins Cth1 and Cth2 play a central role in this translational regulation by repressing the activity of the iron-dependent Rli1 ribosome recycling factor and inhibiting mitochondrial translation and heme biosynthesis. Additionally, we found that iron deficiency represses MRS3 mRNA translation through increased expression of antisense long non-coding RNA. Together, our results reveal complex gene expression and protein synthesis remodeling in response to low iron, demonstrating how this important metal affects protein translation at multiple levels.
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Cell Press
2024-08-30
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Subjects: | Molecular biology, Transcriptomics, molecular biology, transcriptomics, |
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dig-iata-es-10261-3606342024-06-17T20:41:56Z Ribosome profiling reveals the role of yeast RNA-binding proteins Cth1 and Cth2 in translational regulation Barlit, Hanna Romero, Antonia M. Gülhan, Ali Patnaik, Praveen K. Tyshkovskiy, Alexander Martínez-Pastor, María Teresa Gladyshev, Vadim N. Puig, Sergi Labunskyy, Vyacheslav M. Ministerio de Ciencia e Innovación (España) Agencia Estatal de Investigación (España) National Institutes of Health (US) National Institute on Aging (US) Romero, Antonia M. [0000-0002-2727-279X] Martínez-Pastor, María Teresa [0000-0002-4128-958X] Puig, Sergi [0000-0002-1856-490X] Molecular biology Transcriptomics molecular biology transcriptomics Iron serves as a cofactor for enzymes involved in several steps of protein translation, but the control of translation during iron limitation is not understood at the molecular level. Here, we report a genome-wide analysis of protein translation in response to iron deficiency in yeast using ribosome profiling. We show that iron depletion affects global protein synthesis and leads to translational repression of multiple genes involved in iron-related processes. Furthermore, we demonstrate that the RNA-binding proteins Cth1 and Cth2 play a central role in this translational regulation by repressing the activity of the iron-dependent Rli1 ribosome recycling factor and inhibiting mitochondrial translation and heme biosynthesis. Additionally, we found that iron deficiency represses MRS3 mRNA translation through increased expression of antisense long non-coding RNA. Together, our results reveal complex gene expression and protein synthesis remodeling in response to low iron, demonstrating how this important metal affects protein translation at multiple levels. This work was supported by NIH grants AG058713 and AG066704 to V.M.L., and grants PID2020-116940RB-I00 and CEX2021-001189-S from MCIN/AEI/10.13039/501100011033 to S.P. V.N.G. was supported by NIA grants. With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX 2021-001189-S) Peer reviewed 2024-06-17T12:20:54Z 2024-06-17T12:20:54Z 2024-08-30 artículo iScience 27 (6): 109868 (2024) CEX2021-001189-S http://hdl.handle.net/10261/360634 10.1016/j.isci.2024.109868 2589-0042 38779483 2-s2.0-85192993171 https://api.elsevier.com/content/abstract/scopus_id/85192993171 en #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/CEX 2021-001189-S info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-116940RB-I00/ES/MECANISMOS DE ADAPTACION A CONDICIONES NO OPTIMAS DE COBRE Y HIERRO EN LEVADURAS Y PLANTAS / iScience Publisher's version The underlying dataset has been published as supplementary material of the article in the publisher platform at https://doi.org/10.1016/j.isci.2024.109868 https://doi.org/10.1016/j.isci.2024.109868 Sí open application/pdf Cell Press |
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Molecular biology Transcriptomics molecular biology transcriptomics Molecular biology Transcriptomics molecular biology transcriptomics Barlit, Hanna Romero, Antonia M. Gülhan, Ali Patnaik, Praveen K. Tyshkovskiy, Alexander Martínez-Pastor, María Teresa Gladyshev, Vadim N. Puig, Sergi Labunskyy, Vyacheslav M. Ribosome profiling reveals the role of yeast RNA-binding proteins Cth1 and Cth2 in translational regulation |
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Iron serves as a cofactor for enzymes involved in several steps of protein translation, but the control of translation during iron limitation is not understood at the molecular level. Here, we report a genome-wide analysis of protein translation in response to iron deficiency in yeast using ribosome profiling. We show that iron depletion affects global protein synthesis and leads to translational repression of multiple genes involved in iron-related processes. Furthermore, we demonstrate that the RNA-binding proteins Cth1 and Cth2 play a central role in this translational regulation by repressing the activity of the iron-dependent Rli1 ribosome recycling factor and inhibiting mitochondrial translation and heme biosynthesis. Additionally, we found that iron deficiency represses MRS3 mRNA translation through increased expression of antisense long non-coding RNA. Together, our results reveal complex gene expression and protein synthesis remodeling in response to low iron, demonstrating how this important metal affects protein translation at multiple levels. |
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Ministerio de Ciencia e Innovación (España) |
author_facet |
Ministerio de Ciencia e Innovación (España) Barlit, Hanna Romero, Antonia M. Gülhan, Ali Patnaik, Praveen K. Tyshkovskiy, Alexander Martínez-Pastor, María Teresa Gladyshev, Vadim N. Puig, Sergi Labunskyy, Vyacheslav M. |
format |
artículo |
topic_facet |
Molecular biology Transcriptomics molecular biology transcriptomics |
author |
Barlit, Hanna Romero, Antonia M. Gülhan, Ali Patnaik, Praveen K. Tyshkovskiy, Alexander Martínez-Pastor, María Teresa Gladyshev, Vadim N. Puig, Sergi Labunskyy, Vyacheslav M. |
author_sort |
Barlit, Hanna |
title |
Ribosome profiling reveals the role of yeast RNA-binding proteins Cth1 and Cth2 in translational regulation |
title_short |
Ribosome profiling reveals the role of yeast RNA-binding proteins Cth1 and Cth2 in translational regulation |
title_full |
Ribosome profiling reveals the role of yeast RNA-binding proteins Cth1 and Cth2 in translational regulation |
title_fullStr |
Ribosome profiling reveals the role of yeast RNA-binding proteins Cth1 and Cth2 in translational regulation |
title_full_unstemmed |
Ribosome profiling reveals the role of yeast RNA-binding proteins Cth1 and Cth2 in translational regulation |
title_sort |
ribosome profiling reveals the role of yeast rna-binding proteins cth1 and cth2 in translational regulation |
publisher |
Cell Press |
publishDate |
2024-08-30 |
url |
http://hdl.handle.net/10261/360634 https://api.elsevier.com/content/abstract/scopus_id/85192993171 |
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