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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Main Authors: Barlit, Hanna, Romero, Antonia M., Gülhan, Ali, Patnaik, Praveen K., Tyshkovskiy, Alexander, Martínez-Pastor, María Teresa, Gladyshev, Vadim N., Puig, Sergi, Labunskyy, Vyacheslav M.
Other Authors: Ministerio de Ciencia e Innovación (España)
Format: artículo biblioteca
Language:English
Published: Cell Press 2024-08-30
Subjects:Molecular biology, Transcriptomics, molecular biology, transcriptomics,
Online Access:http://hdl.handle.net/10261/360634
https://api.elsevier.com/content/abstract/scopus_id/85192993171
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spelling 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
institution IATA ES
collection DSpace
country España
countrycode ES
component Bibliográfico
access En linea
databasecode dig-iata-es
tag biblioteca
region Europa del Sur
libraryname Biblioteca del IATA España
language English
topic Molecular biology
Transcriptomics
molecular biology
transcriptomics
Molecular biology
Transcriptomics
molecular biology
transcriptomics
spellingShingle 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
description 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.
author2 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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