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

Keith R Mccrae,Zhongwei Li,Ravi Kumar Alluri

doi:10.3389/fmolb.2021.672988

Abstract

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.

Highlights

Cells constantly generate reactive oxygen species as byproducts of oxidative phosphorylation
More than 20 oxidized base lesions have been identified in RNA secondary to the chemical action of Reactive oxygen species (ROS) (Barciszewski et al, 1999) of which 8-hydroxyguanosine (8OHG) is the most prevalent and of considerable importance in many human diseases (Kong and Lin, 2010; Guo et al, 2020; Li et al, 2020) due to its high affinity to pair with all bases (Li et al, 2006)
stress granule (SG) transcriptome studies suggest that only a subset of mRNAs are recruited into the granules without sequence preference, but with enriched longer and less actively translated mRNAs (Kedersha et al, 1999; Kedersha and Anderson, 2002; Khong et al, 2017; Khong and Parker, 2018; Protter and Parker, 2016).These findings indicate that SGs are not sites for general RNA processing but for purposes involving selected RNA molecules

Summary

INTRODUCTION

Cells constantly generate reactive oxygen species as byproducts of oxidative phosphorylation. More than 20 oxidized base lesions have been identified in RNA secondary to the chemical action of ROS (Barciszewski et al, 1999) of which 8-hydroxyguanosine (8OHG) is the most prevalent and of considerable importance in many human diseases (Kong and Lin, 2010; Guo et al, 2020; Li et al, 2020) due to its high affinity to pair with all bases (Li et al, 2006) These chemically modified and oxidized adducts in mRNA lead to the generation of short polypeptides due to premature translation termination (Tanaka et al, 2007) and stalling of ribosomes (Shan et al, 2007). We critically review relevant literature and propose a hypothetical role of SGassociated proteins ADAR1, Tudor-SN, and STAU1, in control of oxidized RNA species that are potentially recruited into SGs

Stress Granules and Their Role in Cellular Functions and Human Diseases

Interaction of Stress Granule and Processing Body

Role of RNA Editing Enzymes in Stress Granules

Oxidized RNAs Accumulate in Stress Granules

Findings

AUTHOR CONTRIBUTIONS