Dynamic 3’UTR Usages in Human Cancers

Talk
Zheng Xia
Baylor College of Medicine
Talk Series: 
Time: 
02.16.2016 11:00 to 12:00
Location: 

AVW 4172

The transcriptome under goes dramatic but highly orchestrated remodeling during diverse physiological state changes such as development and differentiation. This controlled process is perturbed under pathological conditions, such as cancer, leading alterations intranscriptome levels and content. The advent of the RNA-seqhas provided an unprecedented resolutionin profiling different aspects of the transcriptome including alternative splicing, alternative polyadenylation(APA) and longnon-coding RNAs. This form of deep profiling has brought new insights,many of which have been both biologically and clinically relevant.

Recent studies have demonstrated that APA is regulating more than 70% of human genes to have alternative 3’UTR usages. Accumulating evidences have indicated that APA is implicated in human diseases like cancers. Though compelling, it remains to be determined to what extent APA occurs in large clinical cohorts as well as its clinical utilities, functional consequences, and molecular mechanisms. In order to identify APA events retrospectively from the existing large- scaleRNA-seq data sets in The Cancer Genome Atlas (TCGA), I developed a novel bioinformatics tool for the denovo Dynamic analysis of Alternative Poly Adenylationfrom RNA-Seq (DaPars). By applying DaPars to hundreds of tumor-normal matched RNA-seq samples from TCGA, I revealed a globa l3’UTR shortening landscape,which can facilitate up-regulation of oncogenes during tumor igenesisbyescapingmi RNA repression (Xiaetal.,Nature Communications, 2014). Further more,using this method, Iidentified the APA targets of a RNA binding protein CFIm25 as a master APA regulator. Finally, through computational big-data analysis of TCGARNA-sequsing DaPars, Iidentified a pivotal function of CFIm25 as a tumor suppressor in glioblastoma,which was further validated by both invitro and invivo experiments (Masamhaand Xiaetal., Nature, 2014).