RNA Binding Proteins As Regulators of Oxidative Stress Identified by a Targeted CRISPR-Cas9 Single Guide RNA Library

RNA binding proteins fulfil a wide number of roles in gene expression. Multiple mechanisms of RNA binding protein dysregulation have been implicated in the pathomechanisms of several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Oxidative stress and mitochondrial dysfunction also play important roles in these diseases. In this review, we highlight the mechanistic interplay between RNA binding protein dysregulation, oxidative stress and mitochondrial dysfunction in ALS. We also discuss different potential therapeutic strategies targeting these pathways.

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Stress Granule-Mediated Oxidized RNA Decay in P-Body: Hypothetical Role of ADAR1, Tudor-SN, and STAU1

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.672988 ◽

2021 ◽

Vol 8 ◽

Author(s):

Ravi Kumar Alluri ◽

Zhongwei Li ◽

Keith R. McCrae

Keyword(s):

Oxidative Stress ◽

Inverted Repeat ◽

Binding Proteins ◽

Rna Binding ◽

Rna Binding Proteins ◽

Relevant Literature ◽

Stress Granule ◽

P Bodies ◽

Docking Mechanism

Reactive oxygen species (ROS) generated under oxidative stress (OS) cause oxidative damage to RNA. Recent studies have suggested a role for oxidized RNA in several human disorders. Under the conditions of oxidative stress, mRNAs released from polysome dissociation accumulate and initiate stress granule (SG) assembly. SGs are highly enriched in mRNAs, containing inverted repeat (IR) Alus in 3′ UTRs, AU-rich elements, and RNA-binding proteins. SGs and processing bodies (P-bodies) transiently interact through a docking mechanism to allow the exchange of RNA species. However, the types of RNA species exchanged, and the mechanisms and outcomes of exchange are still unknown. Specialized RNA-binding proteins, including adenosine deaminase acting on RNA (ADAR1-p150), with an affinity toward inverted repeat Alus, and Tudor staphylococcal nuclease (Tudor-SN) are specifically recruited to SGs under OS along with an RNA transport protein, Staufen1 (STAU1), but their precise biochemical roles in SGs and SG/P-body docking are uncertain. Here, we critically review relevant literature and propose a hypothetical mechanism for the processing and decay of oxidized-RNA in SGs/P-bodies, as well as the role of ADAR1-p150, Tudor-SN, and STAU1.

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Plasticity of nuclear and cytoplasmic stress responses of RNA-binding proteins

Nucleic Acids Research ◽

10.1093/nar/gkaa256 ◽

2020 ◽

Vol 48 (9) ◽

pp. 4725-4740 ◽

Cited By ~ 3

Author(s):

Michael Backlund ◽

Frank Stein ◽

Mandy Rettel ◽

Thomas Schwarzl ◽

Joel I Perez-Perri ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Stress Responses ◽

Binding Proteins ◽

Rna Binding ◽

Rna Binding Proteins ◽

Environmental Cues ◽

Adaptive Responses ◽

Stressed Cells ◽

And Function

Abstract Cellular stress causes multifaceted reactions to trigger adaptive responses to environmental cues at all levels of the gene expression pathway. RNA-binding proteins (RBP) are key contributors to stress-induced regulation of RNA fate and function. Here, we uncover the plasticity of the RNA interactome in stressed cells, differentiating between responses in the nucleus and in the cytoplasm. We applied enhanced RNA interactome capture (eRIC) analysis preceded by nucleo-cytoplasmic fractionation following arsenite-induced oxidative stress. The data reveal unexpectedly compartmentalized RNA interactomes and their responses to stress, including differential responses of RBPs in the nucleus versus the cytoplasm, which would have been missed by whole cell analyses.

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Cytological analysis of the response of nucleolar RNA and RNA-binding proteins to oxidative stress in HeLa cells

Cell and Tissue Biology ◽

10.1134/s1990519x14060054 ◽

2014 ◽

Vol 8 (6) ◽

pp. 461-472

Author(s):

A. A. Mironova ◽

N. V. Barykina ◽

O. V. Zatsepina

Keyword(s):

Oxidative Stress ◽

Hela Cells ◽

Binding Proteins ◽

Rna Binding ◽

Rna Binding Proteins ◽

Cytological Analysis ◽

Nucleolar Rna

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Cloning and characterization of two guide RNA-binding proteins from mitochondria of Crithidia fasciculata: gBP27, a novel protein, and gBP29, the orthologue of Trypanosoma brucei gBP21

Nucleic Acids Research ◽

10.1093/nar/29.14.2950 ◽

2001 ◽

Vol 29 (14) ◽

pp. 2950-2962 ◽

Cited By ~ 37

Author(s):

D. Blom

Keyword(s):

Trypanosoma Brucei ◽

Binding Proteins ◽

Rna Binding ◽

Rna Binding Proteins ◽

Crithidia Fasciculata ◽

Guide Rna ◽

Novel Protein

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Long Noncoding RNAs and RNA-Binding Proteins in Oxidative Stress, Cellular Senescence, and Age-Related Diseases

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/2062384 ◽

2017 ◽

Vol 2017 ◽

pp. 1-21 ◽

Cited By ~ 30

Author(s):

Chongtae Kim ◽

Donghee Kang ◽

Eun Kyung Lee ◽

Jae-Seon Lee

Keyword(s):

Oxidative Stress ◽

Cell Fate ◽

Cellular Senescence ◽

Binding Proteins ◽

Rna Binding ◽

Rna Binding Proteins ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Age Related ◽

Complex Biological Process

Cellular senescence is a complex biological process that leads to irreversible cell-cycle arrest. Various extrinsic and intrinsic insults are associated with the onset of cellular senescence and frequently accompany genomic or epigenomic alterations. Cellular senescence is believed to contribute to tumor suppression, immune response, and tissue repair as well as aging and age-related diseases. Long noncoding RNAs (lncRNAs) are >200 nucleotides long, poorly conserved, and transcribed in a manner similar to that of mRNAs. They are tightly regulated during various cellular and physiological processes. Although many lncRNAs and their functional roles are still undescribed, the importance of lncRNAs in a variety of biological processes is widely recognized. RNA-binding proteins (RBPs) have a pivotal role in posttranscriptional regulation as well as in mRNA transport, storage, turnover, and translation. RBPs interact with mRNAs, other RBPs, and noncoding RNAs (ncRNAs) including lncRNAs, and they are involved in the regulation of a broad spectrum of cellular processes. Like other cell fate regulators, lncRNAs and RBPs, separately or cooperatively, are implicated in initiation and maintenance of cellular senescence, aging, and age-related diseases. Here, we review the current understanding of both lncRNAs and RBPs and their association with oxidative stress, senescence, and age-related diseases.

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