An Integrative Model for Alternative Polyadenylation, IntMAP, Delineates mTOR-modulated Endoplasmic Reticulum Stress Response

Jae-Woong Chang1,#, Wei Zhang2,3,#, Hsin Sung Yeh1, Meeyeon Park1, Chengguo Yao4, Yongsheng Shi4, Rui Kuang2,* and Jeongsik Yong1,*

1. Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Twin Cities
2. Department of Computer Science and Engineering, University of Minnesota Twin Cities
3. Department of Computer Science, University of Central Florida
4. Department of Microbiology and Molecular Genetics, University of California School of Medicine
# These authors contributed equally to this work
* All correspondence should be addressed to Jeongsik Yong ( and Rui Kuang (


3'-untranslated region (UTR) can vary by alternating polyadenylation sites during pre-mRNA processing. Multiple publically available pipelines combining high profiling technologies and bioinformatics tools have been developed to catalog changes in 3'-UTR lengths. In our recent RNA-seq experiments using cells with hyper-activated mammalian target of rapamycin (mTOR), we found that cellular mTOR activation leads to transcriptome-wide alternative polyadenylation (APA), resulting in the activation of multiple cellular pathways. Here, we developed a novel bioinformatics algorithm, IntMAP, which integrates RNA-Seq and PolyA Site (PAS)-Seq data for a comprehensive characterization of APA events. By applying IntMAP to the datasets from cells with hyper-activated mTOR, we identified novel APA events that could otherwise not be identified by either profiling method alone. Several transcription factors including Cebpg (CCAAT/enhancer binding protein gamma) were among the newly discovered APA transcripts, indicating that diverse transcriptional networks may be regulated by mTOR-coordinated APA. The prevention of APA in Cebpg using the CRISPR/cas9-mediated genome editing tool showed that mTOR-driven 3'-UTR shortening in Cebpg is critical in protecting cells from endoplasmic reticulum (ER) stress. Taken together, we present IntMAP as a new bioinformatics algorithm for APA analysis by which we expand our understanding of the physiological role of mTOR-coordinated APA events to ER stress response.


Funding: This works was supported by National Institutes of Health [1R01GM113952-01A1] and U.S. Army Medical Research and Materiel Command [W81XWH-16-1-0135] to JY, and National Science Foundation [NSF-III1149697] to RK.

Source Code [Matlab code]

Raw Data Set



Processed Data Set


PAS-seq for TSC1-/-

PAS-seq for WT