Volegova et al. 2024 (PRJNA1088608)

General Details

Title Ribosome profiling analysis of neuroblastoma cells in response to amidino-rocaglate treatment
Organism
Number of Samples 12
Release Date 2024/03/15 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP495546
ENA SRP495546
GEO
BioProject PRJNA1088608

Publication

Title
Authors Volegova MP,Brown LE,Banerjee U,Dries R,Sharma B,Kennedy A,Porco JA Jr,George RE
Journal Cell reports
Publication Date 2024 May 28
Abstract Tumor MYCN amplification is seen in high-risk neuroblastoma, yet direct targeting of this oncogenic transcription factor has been challenging. Here, we take advantage of the dependence of MYCN-amplified neuroblastoma cells on increased protein synthesis to inhibit the activity of eukaryotic translation initiation factor 4A1 (eIF4A1) using an amidino-rocaglate, CMLD012824. Consistent with the role of this RNA helicase in resolving structural barriers in 5' untranslated regions (UTRs), CMLD012824 increased eIF4A1 affinity for polypurine-rich 5' UTRs, including that of the MYCN and associated transcripts with critical roles in cell proliferation. CMLD012824-mediated clamping of eIF4A1 spanned the full lengths of mRNAs, while translational inhibition was mediated through 5' UTR binding in a cap-dependent and -independent manner. Finally, CMLD012824 led to growth inhibition in MYCN-amplified neuroblastoma models without generalized toxicity. Our studies highlight the key role of eIF4A1 in MYCN-amplified neuroblastoma and demonstrate the therapeutic potential of disrupting its function. Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
PMC PMC11284644
PMID 38662542
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR28361563 PRJNA1088608 Homo sapiens Neuroblast Ribo-Seq
SRR28361562 PRJNA1088608 Homo sapiens Neuroblast Ribo-Seq
SRR28361561 PRJNA1088608 Homo sapiens Neuroblast Ribo-Seq
SRR28361560 PRJNA1088608 Homo sapiens Neuroblast Ribo-Seq
SRR28361559 PRJNA1088608 Homo sapiens Neuroblast Ribo-Seq
SRR28361558 PRJNA1088608 Homo sapiens Neuroblast Ribo-Seq
SRR28361557 PRJNA1088608 Homo sapiens Neuroblast Ribo-Seq
SRR28361556 PRJNA1088608 Homo sapiens Neuroblast Ribo-Seq
SRR28361555 PRJNA1088608 Homo sapiens Neuroblast Ribo-Seq
SRR28361554 PRJNA1088608 Homo sapiens Neuroblast Ribo-Seq
SRR28361553 PRJNA1088608 Homo sapiens Neuroblast Ribo-Seq
SRR28361552 PRJNA1088608 Homo sapiens Neuroblast 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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