Biased alternative polyadenylation in human tissues

Abstract

Background: Alternative polyadenylation is one of the mechanisms in human cells that give rise to a variety of transcripts from a single gene. More than half of the human genes have multiple polyadenylation sites (poly(A) sites), leading to variable mRNA and protein products. Previous studies of individual genes have indicated that alternative polyadenylation could occur in a tissue-specific manner. Results: We set out to systematically investigate the occurrence and mechanism of alternative polyadenylation in different human tissues using bioinformatic approaches. Using expressed sequence tag (EST) data, we investigated 42 distinct tissue types. We found that several tissues tend to use poly(A) sites that are biased toward certain locations of a gene, such as sites located in introns or internal exons, and various sites in the exon located closest to the 3' end. We also identified several tissues, including eye, retina and placenta, that tend to use poly(A) sites not frequently used in other tissues. By exploring microarray expression data, we analyzed over 20 genes whose protein products are involved in the process or regulation of mRNA polyadenylation. Several brain tissues showed high concordance of gene expression of these genes with each other, but low concordance with other tissue types. By comparing genomic regions surrounding poly(A) sites preferentially used in brain tissues with those in other tissues, we identified several cis-regulatory elements that were significantly associated with brain-specific poly(A) sites. Conclusion: Our results indicate that there are systematic differences in poly(A) site usage among human tissues, and both trans-acting factors and cis-regulatory elements may be involved in regulating alternative polyadenylation in different tissues.