DDX21 at the Nexus of RNA Metabolism, Cancer Oncogenesis, and Host–Virus Crosstalk - Decoding Its Biomarker Potential and Therapeutic Implications

Sep 21, 2026

DDX21, a DEAD-box RNA helicase, is central to RNA metabolism, including ribosomal RNA processing, transcription, and translation. It regulates ribosomal DNA transcription and rRNA processing, and also controls mRNA transcription-related steps such as transcription factor interaction, RNA polymerase II elongation, R-loop binding, and alternative splicing. Elevated DDX21 expression is reported in many cancers, promoting tumorigenesis via effects on ribosome biogenesis, genome stability, and cell-cycle control. It also contributes to antiviral host defense by coordinating with viral proteins, linking its roles across oncology and infection.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Abstract

Introduction

The Structure of DDX21

Review DDX21 at the Nexus of RNA Metabolism, Cancer Oncogenesis, and Host–Virus Crosstalk: Decoding Its Biomarker Potential and Therapeutic Implications Yalan Xiao 1,†, Jiankun Fan 1,†, Zhigang Li 1,* and Yu Hou 1,2, * Citation: Xiao, Y.; Fan, J.; Li, Z.; Hou, Y. DDX21 at the Nexus of RNA Metabolism, Cancer Oncogenesis, and Host–Virus Crosstalk: Decoding Its Biomarker Potential and Therapeutic Implications. Int. J. Mol. Sci. 2024, 25, 13581. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms252413581 Academic Editor: Erik A.C. Wiemer Received: 16 October 2024 Revised: 28 November 2024 Accepted: 11 December 2024 Published: 19 December 2024 Copyright: © 2024 by the authors. 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://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China; [xiao_yalan@stu.cqmu.edu.cn](xiao_yalan@stu.cqmu.edu.cn) (Y.X.); [2021130115@stu.cqmu.edu.cn](2021130115@stu.cqmu.edu.cn) (J.F.) 2 Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing Medical University, Chongqing 400016, China * Correspondence: [zhigang6637@cqmu.edu.cn](zhigang6637@cqmu.edu.cn) (Z.L.); [houyu@cqmu.edu.cn](houyu@cqmu.edu.cn) (Y.H.)† These authors contributed equally to this work. Abstract: DDX21, a member of the DEAD-box RNA helicase family, plays a pivotal role in various aspects of RNA metabolism, including ribosomal RNA (rRNA) processing, transcription, and translation. Its diverse functions in cancer progression and viral infections have attracted considerable attention. DDX21 exerts a pivotal function through ribosomal DNA (rDNA) transcription and rRNA processing. DDX21 is involved in different biological processes of mRNA transcription. It interacts with transcription factors, modulates RNA polymerase II elongation, binds R-loops to regulate transcription, and participates in alternative splicing. The elevated expression of DDX21 has been observed in most cancers, where it influences tumorigenesis by affecting ribosome biogenesis, transcription, genome stability, and cell cycle regulation. Additionally, DDX21 plays a key role in the antiviral defense of host by interacting with viral proteins to regulate essential stages of the infection process. This review provides a thorough examination of the biological functions of DDX21, its involvement in cancer progression and viral infections, and its potential as both a biomarker anda therapeutic target. Future studies should aim to clarify the specific mechanisms of the activity of DDX21, advance the development of targeted therapies, and assess its clinical relevance across various cancer types and stages. Keywords: DDX21; RNA metabolism; cancer biomarker; viral infection 1. Introduction The DEAD-box RNA helicase family, a subset of the helicase superfamily II, is one of the largest helicases families found in eukaryotes, archaea, and bacteria [1] . Characterized by the conserved Asp-Glu-Ala-Asp (DEAD) motif, this family includes 26 members in Saccharomyces cerevisiae and 37 members in Homo sapiens [2,3] . These helicases possess nine conserved motifs responsible for ATP binding and hydrolysis, RNA binding, and ATP-dependent RNA remodeling, which drive their roles in RNA metabolism, such as transcriptional regulation and translation initiation [4–6] . Importantly, these functions are vital for maintaining cell survival. Beyond RNA metabolism, DEAD-box RNA helicases participate in diverse cellular processes, including embryonic development, cell proliferation, hematopoiesis, innate immunity, and immune regulation [5,7,8] . Their involvement extends to pathological c

FAQs

What biological processes does DDX21 regulate in RNA metabolism?

DDX21 is involved in rRNA processing and ribosomal DNA transcription, and it also participates in mRNA transcription regulation through RNA polymerase II elongation, R-loop binding, and alternative splicing.

How is DDX21 linked to cancer progression?

In many cancers, DDX21 is upregulated and influences tumorigenesis by affecting ribosome biogenesis, transcriptional control, genome stability, and cell-cycle regulation.

How does DDX21 contribute to host–virus interactions and antiviral defense?

DDX21 regulates essential stages of infection by interacting with viral proteins, supporting antiviral defense mechanisms during host–virus crosstalk.

Sep 21, 2026

Uploaded by Genevieve