Altered proteome in translation initiation fidelity defective eIF5(G31R) mutant causes oxidative stress and DNA damage

The recognition of the AUG start codon and selection of an open reading frame (ORF) is fundamental to protein biosynthesis. Defect in the fidelity of start codon selection adversely affect proteome and have a pleiotropic effect on cellular function. Using proteomic techniques, we identified differen...

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Autores principales: Ram, Anup Kumar, Mallik, Monalisha, Reddy, R. Rajendra, Suryawanshi, Amol Ratnakar, Alone, Pankaj V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8943034/
https://www.ncbi.nlm.nih.gov/pubmed/35322093
http://dx.doi.org/10.1038/s41598-022-08857-y
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author Ram, Anup Kumar
Mallik, Monalisha
Reddy, R. Rajendra
Suryawanshi, Amol Ratnakar
Alone, Pankaj V.
author_facet Ram, Anup Kumar
Mallik, Monalisha
Reddy, R. Rajendra
Suryawanshi, Amol Ratnakar
Alone, Pankaj V.
author_sort Ram, Anup Kumar
collection PubMed
description The recognition of the AUG start codon and selection of an open reading frame (ORF) is fundamental to protein biosynthesis. Defect in the fidelity of start codon selection adversely affect proteome and have a pleiotropic effect on cellular function. Using proteomic techniques, we identified differential protein abundance in the translation initiation fidelity defective eIF5(G31R) mutant that initiates translation using UUG codon in addition to the AUG start codon. Consistently, the eIF5(G31R) mutant altered proteome involved in protein catabolism, nucleotide biosynthesis, lipid biosynthesis, carbohydrate metabolism, oxidation–reduction pathway, autophagy and re-programs the cellular pathways. The utilization of the upstream UUG codons by the eIF5(G31R) mutation caused downregulation of uridylate kinase expression, sensitivity to hydroxyurea, and DNA damage. The eIF5(G31R) mutant cells showed lower glutathione levels, high ROS activity, and sensitivity to H(2)O(2).
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spelling pubmed-89430342022-03-28 Altered proteome in translation initiation fidelity defective eIF5(G31R) mutant causes oxidative stress and DNA damage Ram, Anup Kumar Mallik, Monalisha Reddy, R. Rajendra Suryawanshi, Amol Ratnakar Alone, Pankaj V. Sci Rep Article The recognition of the AUG start codon and selection of an open reading frame (ORF) is fundamental to protein biosynthesis. Defect in the fidelity of start codon selection adversely affect proteome and have a pleiotropic effect on cellular function. Using proteomic techniques, we identified differential protein abundance in the translation initiation fidelity defective eIF5(G31R) mutant that initiates translation using UUG codon in addition to the AUG start codon. Consistently, the eIF5(G31R) mutant altered proteome involved in protein catabolism, nucleotide biosynthesis, lipid biosynthesis, carbohydrate metabolism, oxidation–reduction pathway, autophagy and re-programs the cellular pathways. The utilization of the upstream UUG codons by the eIF5(G31R) mutation caused downregulation of uridylate kinase expression, sensitivity to hydroxyurea, and DNA damage. The eIF5(G31R) mutant cells showed lower glutathione levels, high ROS activity, and sensitivity to H(2)O(2). Nature Publishing Group UK 2022-03-23 /pmc/articles/PMC8943034/ /pubmed/35322093 http://dx.doi.org/10.1038/s41598-022-08857-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ram, Anup Kumar
Mallik, Monalisha
Reddy, R. Rajendra
Suryawanshi, Amol Ratnakar
Alone, Pankaj V.
Altered proteome in translation initiation fidelity defective eIF5(G31R) mutant causes oxidative stress and DNA damage
title Altered proteome in translation initiation fidelity defective eIF5(G31R) mutant causes oxidative stress and DNA damage
title_full Altered proteome in translation initiation fidelity defective eIF5(G31R) mutant causes oxidative stress and DNA damage
title_fullStr Altered proteome in translation initiation fidelity defective eIF5(G31R) mutant causes oxidative stress and DNA damage
title_full_unstemmed Altered proteome in translation initiation fidelity defective eIF5(G31R) mutant causes oxidative stress and DNA damage
title_short Altered proteome in translation initiation fidelity defective eIF5(G31R) mutant causes oxidative stress and DNA damage
title_sort altered proteome in translation initiation fidelity defective eif5(g31r) mutant causes oxidative stress and dna damage
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8943034/
https://www.ncbi.nlm.nih.gov/pubmed/35322093
http://dx.doi.org/10.1038/s41598-022-08857-y
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