Description:

Bin Tian, PhD
Professor & Center Co-Director
Gene Expression and Regulation Program
Center for Systems and Computational Biology
The Wistar Institute

Almost all eukaryotic mRNAs require cleavage/polyadenylation for 3’ end maturation. Over 70% of mammalian genes harbor multiple cleavage/polyadenylation sites, or PASs, leading to expression of alternative polyadenylation (APA) isoforms. Most APA sites are located in the 3’ most exon, resulting in isoforms with different 3’UTR sizes. 3’UTR APA can play a substantial role in gene expression through regulation of sequence or structure motifs that modulate aspects of mRNA metabolism, such as translation, stability and localization. In addition, about 20% of human genes have APA sites located in introns, which additionally change coding sequences (CDSs), when used. The relative abundance of an APA isoform can vary widely across cell types. For example, neurons tend to express long 3’UTR isoforms, whereas blood cells show the opposite trend. In addition, increased cell proliferation rate was found to be associated with shortening of 3’UTRs through APA, while 3’UTRs lengthen during cell differentiation and development. In this talk, I will review current understanding of gene regulation by APA with a systems biology perspective. I will present our recent finding of unique APA regulation during secretory cell differentiation and data implicating an important role of alternative 3’UTRs in transcript association with endoplasmic reticulum.