Most genes use polyadenylation to maintain the stability of nascent mRNA and to export mRNA to the cytoplasm. This two step process, directed by the polyadenylation signal (PAS), involves cleavage of the 3’ end of the mRNA at the polyadenyation site followed by addition of a polyA tail. The highly conserved canonical hexamer AATAAA and variants of AATAAA are critical elements in facilitating recruitment of cleavage and poladenylation specificity factor (CPSF complex). Variants in these regions have been known to cause disease, but less than less than 30 variants identified have been thought to directly cause Mendelian disease. In this study, we present a set of predominant polyA sites (defined by >50% usage) in protein-coding genes and the corresponding PAS that are most likely to be recognized by the CPSF. Variants in provided PAS can be interrogated for disease studies Variants in PAS can be interrogated for disease studies and the list of predominant polyA sites and signals are available.

Predominant Sites and Signals

Predominant polyA sites and signals were derived from the polyA site 2.0 database. PolyA sites were filtered for protein coding genes. The predominant polyA site was defined as the polyA site that is used in more than 50% of a gene’s transcripts. For each site, predominant polyA signals were selected depending on the strength of the candidate hexamer as well as the distance of the candidate hexamer to the -21 position from representative polyA site. Both files are available in hg38 and hg19.

Predominant PolyA Site file columns

1)  Chromosome 
2)  Predominant polyA hexamer start
3)  Predominant polyA hexamer end
4)  Representative site 
5)  Gene symbol
6)  Strand
7) Annotated location
8) Average TPM of PolyA Site
9) Total average TPM of sites found in Gene
10) PolyA site Usage

Predominant Hexamer bed file columns

1)  Chromosome 
2)  Predominant polyA hexamer start
3)  Predominant polyA hexamer end
4)  Representative site 
5)  Gene symbol
6)  Strand
7)  Hexamer

Clinical Genes

In order to better understand which polyA signal variants are in genes with known clinical significance, we first produced a union of known clinically significant genes found in OMIM, CGD (Clinical Genomics Database), and HGMD. For HGMD, only genes with DM assertion were included. To prevent ambiguity of gene symbols across databases, all gene names were first converted to HGNC IDs before being intersected.

Clinical Genes table columns

1)  Ensembl Gene Symbol
2)  Found in OMIM?
3)  Found in HGMD?
4)  Found in CGD?
5)  Has predominant polyA signal?