Uncovering the Multifaceted Roles of DDX21: Bridging Biological Insights and Medical Applications

Abstract

DDX21 belongs to the DEAD-box (DDX) family of helicases but deviates from the characteristic sequence Asp–Glu–Ala–Asp (DEAD) to Asp–Glu–Val–Asp. In addition to the typical helicase activity associated with the DEAD-box family, DDX21 also possesses foldase and adenosine triphosphatase activities. It plays crucial roles in various molecular processes, including the regulation of transcription, ribosomal RNA processing, modification, and unwinding of RNA spatial structures. DDX21 is subject to intricate regulation by multiple upstream factors, including expression control and posttranslational modification. In numerous cancer types, abnormal expression of DDX21 has been observed to influence cancer cell behaviors, such as the cell cycle, proliferation, invasion, migration, and apoptosis. In addition, DDX21 modulates innate immunity following viral infection and plays a dual role in the viral infection process. This review comprehensively explores the protein structure, molecular regulatory mechanisms, and pathophysiological functions of DDX21. Consequently, this study not only offers potential avenues for future research but also sparks novel ideas for targeted treatments for both cancer and viral infections.