Datasets

Title	Multiplexed functional genomic analysis of somatic 5' untranslated region mutations across the spectrum of human prostate cancer (Ribosome Profiling)
Organism
Number of Samples	10
Release Date	2019/04/29 00:00
Sequencing Types
Protocol Details

Title
Authors	Lim Y,Arora S,Schuster SL,Corey L,Fitzgibbon M,Wladyka CL,Wu X,Coleman IM,Delrow JJ,Corey E,True LD,Nelson PS,Ha G,Hsieh AC
Journal	Nature communications
Publication Date	2021 Jul 9
Abstract	The functional consequences of genetic variants within 5' untranslated regions (UTRs) on a genome-wide scale are poorly understood in disease. Here we develop a high-throughput multi-layer functional genomics method called PLUMAGE (Pooled full-length UTR Multiplex Assay on Gene Expression) to quantify the molecular consequences of somatic 5' UTR mutations in human prostate cancer. We show that 5' UTR mutations can control transcript levels and mRNA translation rates through the creation of DNA binding elements or RNA-based cis-regulatory motifs. We discover that point mutations can simultaneously impact transcript and translation levels of the same gene. We provide evidence that functional 5' UTR mutations in the MAP kinase signaling pathway can upregulate pathway-specific gene expression and are associated with clinical outcomes. Our study reveals the diverse mechanisms by which the mutational landscape of 5' UTRs can co-opt gene expression and demonstrates that single nucleotide alterations within 5' UTRs are functional in cancer. © 2021. The Author(s).
PMC	PMC8270899
PMID	34244513
DOI

Lim et al. 2021 (PRJNA540298)