Transcriptomics

Dataset Information

299

Transcription profiling by high throughput sequencing of KOPT-K1 cells treated with silvestrol


ABSTRACT: The translational control of oncoprotein expression is implicated in many cancers. Here we report an eIF4A/DDX2 RNA helicase-dependent mechanism of translational control that contributes to oncogenesis and underlies the anticancer effects of Silvestrol and related compounds. For example, eIF4A promotes T-ALL development in vivo and is required for leukaemia maintenance. Accordingly, inhibition of eIF4A with Silvestrol has powerful therapeutic effects in vitro and in vivo. We use transcriptome-scale ribosome footprinting to identify the hallmarks of eIF4A-dependent transcripts. These include 5'UTR sequences such as the 12-mer guanine quartet (CGG)4 motif that can form RNA G-quadruplex structures. Notably, among the most eIF4A-dependent and Silvestrol-sensitive transcripts are a number of oncogenes, super-enhancer associated transcription factors, and epigenetic regulators. Hence, the 5'UTRs of selected cancer genes harbour a targetable requirement for the eIF4A RNA helicase. Comparison of ribosome-protected RNA for drug treated and DMSO treated KOPT-K1 cell, two replicates of ribosome-protected RNA sequencing and three replicates of RNA-seq.

REANALYSED by: E-GEOD-56887

ORGANISM(S): Homo sapiens  

SUBMITTER: Jerry Pelletier   Man Jiang  Chunying Zhao  Michelle A Kelliher  Justine E Roderick  Frank Speleman  Hans-Guido Wendel  Vinagolu K Rajasekhar  Gunnar Rätsch  Kamini Singh  Jonathan H Schatz  Christina M Rodrigo  Andrew L Wolfe  Philipp Drewe  Konstantinos J Mavrakis  Yi Zhong  Pieter Rondou  John A Porco Jr.  Viraj R Sanghvi  Joni Van der Meulen  Elisa de Stanchina  Julie Teruya-Feldstein 

PROVIDER: E-GEOD-56887 | ArrayExpress | 2014-07-27

SECONDARY ACCESSION(S): GSE56887SRP041255PRJNA244865

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications


The translational control of oncoprotein expression is implicated in many cancers. Here we report an eIF4A RNA helicase-dependent mechanism of translational control that contributes to oncogenesis and underlies the anticancer effects of silvestrol and related compounds. For example, eIF4A promotes T-cell acute lymphoblastic leukaemia development in vivo and is required for leukaemia maintenance. Accordingly, inhibition of eIF4A with silvestrol has powerful therapeutic effects against murine and  ...[more]

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