Koret-Berkeley-Tel Aviv-Initiative in Computational Biology: A webinar

Online event


20:00 (Israel time)


Zoom linkhttps://berkeley.zoom.us/j/91230131804



26 January 2021, 20:00 
Online webinar - https://berkeley.zoom.us/j/91230131804 
Koret-Berkeley-Tel Aviv-Initiative in Computational Biology: A webinar

Koret-Berkeley-Tel Aviv-Initiative in Computational Biology: A webinar


Part of the joint seminar series of the Koret-Berkeley-Tel Aviv University Initiative in Computational Biology and Bioinformatics.


Prof. Ran Elkon, Principal Investigator

Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University


"Systematic exploration of gene regulation by 3’UTR alternative polyadenylation"


Please join us Tuesday, 26 January 2021 at 8pm Israel time (10am PT)


Webinar linkhttps://berkeley.zoom.us/j/91230131804



Abstract: Alternative polyadenylation (APA) is emerging as a widespread regulatory layer because the majority of human protein-coding genes were demonstrated to contain several polyadenylation (p(A)) sites in their 3'UTRs. By generating isoforms with different 3'UTR length, APA potentially affects mRNA stability, translation efficiency, nuclear export, and cellular localization. Yet, our understanding of how APA is modulated and of its roles in various biological processes remains rudimentary. In my talk I will present two recent studies in which we explored APA on a genomic scale. In the first study, we developed a bioinformatics method for analysis of APA from single-cell 3’-end RNA-seq data. Analyzing multiple scRNA-seq datasets from diverse tissues, we identified widespread modulation of APA in different cell types resulting in global 3' UTR shortening/lengthening and enhanced cleavage at cryptic pA sites within introns. In the second study we systematically explored the impact of common genetic variation on APA. Polyadenylation sites are regulated by adjacent RNA cis-regulatory elements, the principals among them are the polyadenylation signal (PAS) AAUAAA and its main variant AUUAAA, typically located ~20-nt upstream of the p(A) site. We searched for common SNPs that affect gene expression and human traits by modulation of 3'UTR APA. First, focusing on the variants most likely to exert the strongest effect, we identified 2,305 SNPs that interrupt the canonical PAS or its main variant. Implementing pA-QTL tests using GTEx RNA-seq data, we identified 330 PAS SNPs (which we termed PAS pA-QTLs) that were significantly associated with the usage of their p(A) site. As expected, PAS-interrupting alleles were mostly linked with decreased cleavage at their p(A) site and the consequential 3'UTR lengthening. As an indication of the functional effects of these PAS pA-QTLs on gene expression and complex human traits, we observed for few dozens of them marked colocalization with eQTL and/or GWAS signals. The PAS-interrupting alleles linked with 3'UTR lengthening were also strongly associated with decreased gene expression, indicating that shorter isoforms generated by APA are generally more stable than longer ones. Last, we carried out an extended, genome-wide analysis of 3'UTR variants and detected thousands of additional pA-QTLs having weaker effects compared to the PAS pA-QTLs. 



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