Research Grants 22/12010-0 - Biologia estrutural, RNA helicases - BV FAPESP
Advanced search
Start date
Betweenand

Investigation of human RNA helicase DDX3X and its process of phase separation (LLPS) through mutations identified in patients with neurodevelopmental disorders

Abstract

Neurodevelopmental disorders (NDD) constitute a set of clinical conditionscharacterized by disturbances during brain development, among the most common areautism spectrum disorder (ASD) and intellectual disability (ID). To extend the comprehensionabout the molecular mechanisms related to these disorders, this research project proposesto study an important human RNA helicase from DEAD-box family, DDX3X, highly associatedwith ASD and ID, through genetic mutations identified in patients with NDDs. DDX3X isinvolved in several steps of RNA metabolism, essential for the correct neural development,and essential for liquid-liquid phase separation (LLPS), being also target for other humandiseases as cancer (leukemia, lymphoma) and viruses (HIV, dengue, SARS-CoV-2). The aimof this project is to study five missense mutations in DDX3X identified in patients with ID and ASD to analyze the impact on protein structure/function relationship. Our previous works have shown that disease-related genetic mutations are powerful tools to understand the action mechanism of important human proteins in atomic level. In this project, recombinant DDX3Xwill be produced to perform enzymatic assays, aiming to comprehend the impact of mutationsin DDX3X activity; biophysical studies, to characterize mutants and its interactions withsubstrates (RNA and ATP); structural studies using X ray crystallography, NMR and electroncryo-microscopy to investigate the mechanisms involved in protein activity; and LLPSformation in vitro and in cell by image techniques, to check if mutations interfere in this important cellular process. In summary, this project intends to increase the comprehensionabout the functioning of an important human protein associated with pathological disordersand essential for cellular phase separation process, to promote the knowledge about themolecular mechanisms related to NDDs and aiming to contribute to the future developmentof molecules that can act as chemical probes or drugs for ID and ASD. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
More itemsLess items
Articles published in other media outlets ( ):
More itemsLess items
VEICULO: TITULO (DATA)
VEICULO: TITULO (DATA)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SILVA, IVAN ROSA E; SMETANA, JULIANA HELENA COSTA; DE OLIVEIRA, JULIANA FERREIRA. A comprehensive review on DDX3X liquid phase condensation in health and neurodevelopmental disorders. International Journal of Biological Macromolecules, v. 259, p. 15-pg., . (22/12010-0)

Please report errors in scientific publications list using this form.
X

Report errors in this page


Error details: