ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2016
DDX3 Modulates Neurite Development via Translationally Activating an RNA Regulon Involved in Rac1 Activation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 62 citations in OpenAlex.
- DDX3 inhibits PTZ-induced ferroptosis in human neuronal SH-SY5Y cells via Wnt/β-catenin signaling.In vitro cellular & developmental biology. Animal · 2026Article
- Knockdown of Ddx3x in mPFC induces autistic-like phenotype in mice via altered synaptic plasticity.Translational psychiatry · 2026Article
- Methylone promotes neurite outgrowth and has long-lasting effects on fear extinction learning.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Targeting FAM134B-DDX3X axis inhibiting AKT signaling in hepatocellular carcinoma.Cell death & disease · 2025Article
- Exploration of a DDX3X Gene Supplementation Therapy Including Expanded Characterization and Novel Findings of Sleep Disturbances inBiological psychiatry global open science · 2025Article
- Impaired cortical development and translational control in a missense mouse model of DDX3X syndrome.Disease models & mechanisms · 2025Article
- Unveiling the reproductive risks of PFOS: testicular proteome disruption and hormonal imbalance in male rats†.Biology of reproduction · 2025Article
- Regulatory role of the N-terminal intrinsically disordered region of the DEAD-box RNA helicase DDX3X in selective RNA recognition.Nature communications · 2025Article
- Sex-specific perturbations of neuronal development caused by mutations in the autism risk gene DDX3X.Nature communications · 2025Article
- DEAD/DEAH-box RNA helicases shape the risk of neurodevelopmental disorders.Trends in genetics : TIG · 2025Review
- O-GlcNAcylation of the intellectual disability protein DDX3X exerts proteostatic cell cycle control.Open biology · 2025Article
- DEAD-box helicase family proteins: emerging targets in digestive system cancers and advances in targeted drug development.Journal of translational medicine · 2024Review
- DDX3 is critical for female fertility via translational control in oogenesis.Cell death discovery · 2024Article
- Deficiency ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- A novel reporter for helicase activity in translation uncovers DDX3X interactions.RNA (New York, N.Y.) · 2024Article
- The Role of the RNA Helicase DDX3X in Medulloblastoma Progression.Biomolecules · 2024Review
- Overexpression of olfactory receptor 78 ameliorates brain injury in cerebral ischaemia-reperfusion rats by activating Prkaca-mediated cAMP/PKA-MAPK pathway.Journal of cellular and molecular medicine · 2024Article
- MiR-181a-5p knockdown ameliorates sevoflurane anesthesia-induced neuron injury via regulation of the DDX3X/Wnt/β-catenin signaling axis.Experimental brain research · 2024Article
- Network Analysis Performed on Transcriptomes of Parkinson's Disease Patients Reveals Dysfunction in Protein Translation.International journal of molecular sciences · 2024Article
- The mRNA-binding protein DDX3 mediates TGF-β1 upregulation of translation and promotes pulmonary fibrosis.JCI insight · 2023Article
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Authors and funding
3 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
unlabelledThe RNA helicase DDX3 is a component of neuronal granules, and its gene mutations are linked to intellectual disability (ID). Here we demonstrate that DDX3 depletion in neurons impairs neurite development by downregulating Rac1 level and activation. Moreover, DDX3 activates the translation of functionally coherent mRNAs involved in Rac1 activation including Rac1 Among the DDX3 regulon, Prkaca encodes the catalytic subunit of PKA, a potential activator of Rac1 in neurons. DDX3-modulated PKAcα and Rac1 expression tunes the strength of PKA-Rac1 signaling and thereby contributes to neurite outgrowth and dendritic spine formation. Inhibition of DDX3 activity or expression in neonatal mice impaired dendritic outgrowth and spine formation of hippocampal neurons, echoing neuronal deficits underling DDX3 mutation-associated ID. Finally, we provide evidence that DDX3 activates local protein synthesis through a 5' UTR-dependent mechanism in neurons. The novel DDX3 regulon may conduct a spatial and temporal control of Rac1 signaling to regulate neurite development. SIGNIFICANCE STATEMENT: DDX3X mutations are linked to intellectual disability (ID). We provide first evidence that DDX3 is required for neurite outgrowth and dendritic spine formation in vitro and in vivo We identified a DDX3 regulon constituting functionally cohesive mRNAs involved in Rac1 signaling, which contributes to DDX3-modulated neurite development. Inhibition or ablation of DDX3 in vivo shortened neurite lengths and impaired dendritic spine formation in hippocampal neurons, reflecting the prevalence of ID-associated DDX3X mutations in the helicase domain. Mechanistically, DDX3 activates local protein synthesis of mRNAs sharing similar 5' UTR structures and therefore controls Rac1 signaling strength in neurites.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.