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RNA G-Quadruplex within the 5′-UTR of FEN1 Regulates mRNA Stability under Oxidative Stress

Reactive oxygen species (ROS) are a group of highly oxidative molecules that induce DNA damage, affecting DNA damage response (DDR) and gene expression. It is now recognized that DNA base excision repair (BER) is one of the important pathways responsible for sensing oxidative stress to eliminate DNA...

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Autores principales: Ma, Ying, Yang, Yang, Xin, Jingyu, He, Lingfeng, Hu, Zhigang, Gao, Tao, Pan, Feiyan, Guo, Zhigang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9952066/
https://www.ncbi.nlm.nih.gov/pubmed/36829835
http://dx.doi.org/10.3390/antiox12020276
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author Ma, Ying
Yang, Yang
Xin, Jingyu
He, Lingfeng
Hu, Zhigang
Gao, Tao
Pan, Feiyan
Guo, Zhigang
author_facet Ma, Ying
Yang, Yang
Xin, Jingyu
He, Lingfeng
Hu, Zhigang
Gao, Tao
Pan, Feiyan
Guo, Zhigang
author_sort Ma, Ying
collection PubMed
description Reactive oxygen species (ROS) are a group of highly oxidative molecules that induce DNA damage, affecting DNA damage response (DDR) and gene expression. It is now recognized that DNA base excision repair (BER) is one of the important pathways responsible for sensing oxidative stress to eliminate DNA damage, in which FEN1 plays an important role in this process. However, the regulation of FEN1 under oxidative stress is still unclear. Here, we identified a novel RNA G-quadruplex (rG4) sequence in the 5′untranslated region (5′UTR) of FEN1 mRNA. Under oxidative stress, the G bases in the G4-forming sequence can be oxidized by ROS, resulting in structural disruption of the G-quadruplex. ROS or TMPyP4, a G4-structural ligand, disrupted the formation of G4 structure and affected the expression of FEN1. Furthermore, pull-down experiments identified a novel FEN1 rG4-binding protein, heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), and cellular studies have shown that hnRNPA1 plays an important role in regulating FEN1 expression. This work demonstrates that rG4 acts as a ROS sensor in the 5′UTR of FEN1 mRNA. Taken together, these results suggest a novel role for rG4 in translational control under oxidative stress.
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spelling pubmed-99520662023-02-25 RNA G-Quadruplex within the 5′-UTR of FEN1 Regulates mRNA Stability under Oxidative Stress Ma, Ying Yang, Yang Xin, Jingyu He, Lingfeng Hu, Zhigang Gao, Tao Pan, Feiyan Guo, Zhigang Antioxidants (Basel) Article Reactive oxygen species (ROS) are a group of highly oxidative molecules that induce DNA damage, affecting DNA damage response (DDR) and gene expression. It is now recognized that DNA base excision repair (BER) is one of the important pathways responsible for sensing oxidative stress to eliminate DNA damage, in which FEN1 plays an important role in this process. However, the regulation of FEN1 under oxidative stress is still unclear. Here, we identified a novel RNA G-quadruplex (rG4) sequence in the 5′untranslated region (5′UTR) of FEN1 mRNA. Under oxidative stress, the G bases in the G4-forming sequence can be oxidized by ROS, resulting in structural disruption of the G-quadruplex. ROS or TMPyP4, a G4-structural ligand, disrupted the formation of G4 structure and affected the expression of FEN1. Furthermore, pull-down experiments identified a novel FEN1 rG4-binding protein, heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), and cellular studies have shown that hnRNPA1 plays an important role in regulating FEN1 expression. This work demonstrates that rG4 acts as a ROS sensor in the 5′UTR of FEN1 mRNA. Taken together, these results suggest a novel role for rG4 in translational control under oxidative stress. MDPI 2023-01-26 /pmc/articles/PMC9952066/ /pubmed/36829835 http://dx.doi.org/10.3390/antiox12020276 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ma, Ying
Yang, Yang
Xin, Jingyu
He, Lingfeng
Hu, Zhigang
Gao, Tao
Pan, Feiyan
Guo, Zhigang
RNA G-Quadruplex within the 5′-UTR of FEN1 Regulates mRNA Stability under Oxidative Stress
title RNA G-Quadruplex within the 5′-UTR of FEN1 Regulates mRNA Stability under Oxidative Stress
title_full RNA G-Quadruplex within the 5′-UTR of FEN1 Regulates mRNA Stability under Oxidative Stress
title_fullStr RNA G-Quadruplex within the 5′-UTR of FEN1 Regulates mRNA Stability under Oxidative Stress
title_full_unstemmed RNA G-Quadruplex within the 5′-UTR of FEN1 Regulates mRNA Stability under Oxidative Stress
title_short RNA G-Quadruplex within the 5′-UTR of FEN1 Regulates mRNA Stability under Oxidative Stress
title_sort rna g-quadruplex within the 5′-utr of fen1 regulates mrna stability under oxidative stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9952066/
https://www.ncbi.nlm.nih.gov/pubmed/36829835
http://dx.doi.org/10.3390/antiox12020276
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