A comprehensive review on DDX3X liquid phase condensation in health and neurodevelopmental disorders

Author(s)

Silva, Ivan Rosa e ; Smetana, Juliana Helena Costa ; de Oliveira, Juliana Ferreira

• Document type: Journal article
• Source: International Journal of Biological Macromolecules; v. 259, p. 15-pg., 2024-01-16.

Abstract

DEAD-box helicases are global regulators of liquid-liquid phase separation (LLPS), a process that assembles membraneless organelles inside cells. An outstanding member of the DEAD-box family is DDX3X, a multifunctional protein that plays critical roles in RNA metabolism, including RNA transcription, splicing, nucleocytoplasmic export, and translation. The diverse functions of DDX3X result from its ability to bind and remodel RNA in an ATP-dependent manner. This capacity enables the protein to act as an RNA chaperone and an RNA helicase, regulating ribonucleoprotein complex assembly. DDX3X and its orthologs from mouse, yeast (Ded1), and C. elegans (LAF-1) can undergo LLPS, driving the formation of neuronal granules, stress granules, processing bodies or P-granules. DDX3X has been related to several human conditions, including neurodevelopmental disorders, such as intellectual disability and autism spectrum disorder. Although the research into the pathogenesis of aberrant biomolecular condensation in neurodegenerative diseases is increasing rapidly, the role of LLPS in neurodevelopmental disorders is underexplored. This review summarizes current findings relevant for DDX3X phase separation in neurodevelopment and examines how disturbances in the LLPS process can be related to neurodevelopmental disorders. (AU)

• FAPESP's process: 22/12010-0 - Investigation of human RNA helicase DDX3X and its process of phase separation (LLPS) through mutations identified in patients with neurodevelopmental disorders
• Grantee: Juliana Ferreira de Oliveira
• Support Opportunities: Regular Research Grants