The DEAD-Box RNA Helicase DDX3 Interacts with m6A RNA Demethylase ALKBH5.

Ge Shan,Shanshan Hu,Liang Chen,Abdullah Shah,Xiaolin Wang,Farooq Rashid,Hassaan Mehboob Awan

doi:10.1155/2017/8596135

Abstract

DDX3 is a member of the family of DEAD-box RNA helicases. DDX3 is a multifaceted helicase and plays essential roles in key biological processes such as cell cycle, stress response, apoptosis, and RNA metabolism. In this study, we found that DDX3 interacted with ALKBH5, an m6A RNA demethylase. The ATP domain of DDX3 and DSBH domain of ALKBH5 were indispensable to their interaction with each other. Furthermore, DDX3 could modulate the demethylation of mRNAs. We also showed that DDX3 regulated the methylation status of microRNAs and there was an interaction between DDX3 and AGO2. The dynamics of m6A RNA modification is still a field demanding further investigation, and here, we add a link by showing that RNA demethylation can be regulated by proteins such as DDX3.

Highlights

DEAD- (Asp-Glu-Ala-Asp-) box (DDX) proteins are the largest family of RNA helicases [1]
IP of DDX3 could co-IP AlkB homolog 5 (ALKBH5) (Figure 1(f)). These data demonstrated that ALKBH5 was the only protein among the five methyltransferases and demethylases that interacted with DDX3
We found that DDX3 interacted with ALKBH5, an RNA m6A demethylase

Summary

Introduction

DEAD- (Asp-Glu-Ala-Asp-) box (DDX) proteins are the largest family of RNA helicases [1] This family plays pleiotropic functions in cells by an interaction with other proteins or different forms of RNA, to maintain the integrity of the secondary and tertiary structure of RNAs and facilitate multiple RNA processing procedures [1,2,3]. These helicases contain a highly conserved catalytic core domain that mediates the ATPase and helicase activities as well as the less conserved N and C-termini, which are thought to confer functional specificity and subcellular localization of individual DDX helicases [4,5,6]. Multiple lines of evidence suggest that specific cofactors can modify the functionality of DDX3, such as DDX3 forms functional complex with the transcription factor SP1 (specificity protein 1) and enhances the expression activity of its cognate promoters [16]

Methods

Results

Conclusion