Oh et al. 2016 (PRJNA289569)

General Details

Title Profiles of ribosome-associated mRNAs regulated by expression of wild-type (WT) or R534H variant of DDX3 with or without Sodium Arsenite treatment [Ribo-Seq]
Organism
Number of Samples 12
Release Date 2015/07/11 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP060676
ENA SRP060676
GEO
BioProject PRJNA289569

Publication

Title
Authors Oh S,Flynn RA,Floor SN,Purzner J,Martin L,Do BT,Schubert S,Vaka D,Morrissy S,Li Y,Kool M,Hovestadt V,Jones DT,Northcott PA,Risch T,Warnatz HJ,Yaspo ML,Adams CM,Leib RD,Breese M,Marra MA,Malkin D,Lichter P,Doudna JA,Pfister SM,Taylor MD,Chang HY,Cho YJ
Journal Oncotarget
Publication Date 2016 May 10
Abstract 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 with a general reduction of translation, and both the shift of DDX3 on mRNA and decreased translation are blunted by expression of a catalytically-impaired, medulloblastoma-associated DDX3R534H variant. Furthermore, despite the global repression of translation induced by arsenite, translation is preserved on select genes involved in chromatin organization in DDX3R534H-expressing cells. Thus, DDX3 interacts extensively with RNA and ribosomal machinery to help remodel the translation landscape in response to stress, while cancer-related DDX3 variants adapt this response to selectively preserve translation.
PMC PMC5053718
PMID 27058758
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR2096964 PRJNA289569 Homo sapiens HEK293 Ribo-Seq
SRR2096965 PRJNA289569 Homo sapiens HEK293 Ribo-Seq
SRR2096966 PRJNA289569 Homo sapiens HEK293 Ribo-Seq
SRR2096967 PRJNA289569 Homo sapiens HEK293 Ribo-Seq
SRR2096968 PRJNA289569 Homo sapiens HEK293 Ribo-Seq
SRR2096969 PRJNA289569 Homo sapiens HEK293 Ribo-Seq
SRR2096970 PRJNA289569 Homo sapiens HEK293 Ribo-Seq
SRR2096971 PRJNA289569 Homo sapiens HEK293 Ribo-Seq
SRR2096972 PRJNA289569 Homo sapiens HEK293 Ribo-Seq
SRR2096973 PRJNA289569 Homo sapiens HEK293 Ribo-Seq
SRR2096974 PRJNA289569 Homo sapiens HEK293 Ribo-Seq
SRR2096975 PRJNA289569 Homo sapiens HEK293 Ribo-Seq
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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