Open AccessPathway-guided analysis identifies Myc-dependent alternative pre-mRNA splicing in aggressive prostate cancers
Author(s) -
John W. Phillips,
Yang Pan,
Brandon L. Tsai,
Zhijie Xie,
Levon Demirdjian,
Wen Xiao,
Haiou Yang,
Yida Zhang,
Chia Ho Lin,
Donghui Cheng,
Qiang Hu,
Song Liu,
Douglas L. Black,
Owen N. Witte,
Yi Xing
Publication year - 2020
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1915975117
Subject(s) - exon , rna splicing , biology , alternative splicing , exon skipping , computational biology , rna , gene , genetics , messenger rna , cancer research
Significance Alternative pre-mRNA splicing is a regulated process that greatly diversifies gene products by changing the exons incorporated into mRNA. This process is dysregulated in cancers. Here, we studied exon usage in aggressive prostate cancers and linked exon incorporation decisions to cancer driver genes. Through computational and experimental studies, we found that a strong cancer driver gene, Myc, was linked to exon changes in genes that themselves regulate alternative splicing. These exons often encoded premature stop codons that would decrease gene expression, suggestive of a Myc-driven autoregulatory loop to help control levels of splicing regulatory proteins.