biostudies-literatureOh SNCI NIH HHSNIGMS NIH HHS28169-82https://www.ebi.ac.uk/biostudies/studies/S-EPMC5053718biostudies-literatureUnknown7(19)DDX3X encodes a DEAD-box family RNA helicase (DDX3) commonly mutated in medulloblastoma, a highly aggressive cerebellar tumor affecting both children and adults. Despite being implicated in several facets of RNA metabolism, the nature and scope of DDX3's interactions with RNA remain unclear. Here, we show DDX3 collaborates extensively with the translation initiation machinery through direct binding to 5'UTRs of nearly all coding RNAs, specific sites on the 18S rRNA, and multiple components of the translation initiation complex. Impairment of translation initiation is also evident in primary medulloblastomas harboring mutations in DDX3X, further highlighting DDX3's role in this process. Arsenite-induced stress shifts DDX3 binding from the 5'UTR into the coding region of mRNAs concomitant wiOncotargetMedulloblastoma-associated DDX3 variant selectively alters the translational response to stress.PMC5053718U01 CA176287P50 GM102706Morrissy SKool MPurzner JLeib RDOh SSchubert SVaka DPfister SMMartin LMarra MADo BTJones DTTaylor MDHovestadt VFloor SNDoudna JANorthcott PAChang HYCho YJYaspo MLMalkin DAdams CMLichter PFlynn RALi YWarnatz HJRisch TBreese MfalseMedulloblastoma-associated DDX3 variant selectively alters the translational response to stress.DDX3X encodes a DEAD-box family RNA helicase (DDX3) commonly mutated in medulloblastoma, a highly aggressive cerebellar tumor affecting both children and adults. Despite being implicated in several facets of RNA metabolism, the nature and scope of DDX3's interactions with RNA remain unclear. Here, we show DDX3 collaborates extensively with the translation initiation machinery through direct binding to 5'UTRs of nearly all coding RNAs, specific sites on the 18S rRNA, and multiple components of the translation initiation complex. Impairment of translation initiation is also evident in primary medulloblastomas harboring mutations in DDX3X, further highlighting DDX3's role in this process. Arsenite-induced stress shifts DDX3 binding from the 5'UTR into the coding region of mRNAs concomitant wi2016-01-01T00:00:00Z2016 May2026-04-29T09:44:02.033Z2026-04-07T15:04:52.956ZS-EPMC50537182705875810.18632/oncotarget.8612