Multiple functions of DDX3 RNA helicase in gene regulation, tumorigenesis, and viral infection.

Yasuo Ariumi

doi:10.3389/fgene.2014.00423

Abstract

The DEAD-box RNA helicase DDX3 is a multifunctional protein involved in all aspects of RNA metabolism, including transcription, splicing, mRNA nuclear export, translation, RNA decay and ribosome biogenesis. In addition, DDX3 is also implicated in cell cycle regulation, apoptosis, Wnt-β-catenin signaling, tumorigenesis, and viral infection. Notably, recent studies suggest that DDX3 is a component of anti-viral innate immune signaling pathways. Indeed, DDX3 contributes to enhance the induction of anti-viral mediators, interferon (IFN) regulatory factor 3 and type I IFN. However, DDX3 seems to be an important target for several viruses, such as human immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV), hepatitis B virus (HBV), and poxvirus. DDX3 interacts with HIV-1 Rev or HCV Core protein and modulates its function. At least, DDX3 is required for both HIV-1 and HCV replication. Therefore, DDX3 could be a novel therapeutic target for the development of drug against HIV-1 and HCV.

Highlights

DDX3 belongs to the DEAD (D-E-A-D: Asp-Glu-Ala-Asp)-box RNA helicase family, which is an ATPase-dependent RNA helicase, is found in various organisms from yeast to human (Cordin et al, 2006; Linder and Lasko, 2006; Linder, 2008; Jankowsky, 2011)
DDX3X is ubiquitously expressed in most tissues, while the expression of DDX3Y protein is limited to the male germline (Ditton et al, 2004) and DDX3Y seems to be involved in male fertility (Leory et al, 1989; Mazeyrat et al, 1998; Foresta et al, 2000)
DDX3 interacts with two nuclear export shuttle protein: CRM1 as a receptor for protein containing the nuclear export signal (NES) and tip-associated protein (TAP) as the major receptor for mRNA export (Yedavalli et al, 2004; Lai et al, 2008)

Summary

Yasuo Ariumi*

Ariumi Project Laboratory, Center for AIDS Research – International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan. Reviewed by: Kaoru Tominaga, Jichi Medical University, Japan Victoria V. Recent studies suggest that DDX3 is a component of anti-viral innate immune signaling pathways. DDX3 contributes to enhance the induction of anti-viral mediators, interferon (IFN) regulatory factor 3 and type I IFN. DDX3 seems to be an important target for several viruses, such as human immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV), hepatitis B virus (HBV), and poxvirus. DDX3 interacts with HIV-1 Rev or HCV Core protein and modulates its function. DDX3 is required for both HIV-1 and HCV replication. DDX3 could be a novel therapeutic target for the development of drug against HIV-1 and HCV

INTRODUCTION

Findings

Vaccinia virus ?