Abstract The cleavage and polyadenylation site (PAS) defines the 3′ end of almost all protein-coding and long non-coding RNAs in eukaryotes. Most genes harbor multiple PAS, resulting in expression of alternative polyadenylation (APA) isoforms. Here, we present PolyADB version 4 (https: //exon. apps. wistar. org/polyadb/v4/), an updated database dedicated to PAS in mammalian genomes. By exhaustive mining of human and mouse transcriptomic data sets generated by the 3′ region extraction and deep sequencing plus (3'READS+) method, corresponding to ∼2. 3 billion PAS-supporting reads for each species, we identify ∼1. 4 million PAS in both human and mouse genomes, increasing PAS coverage over the last database version by 4. 9- and 3. 5-fold, respectively. Of the full PAS set (named Max collection), 20% of them match the transcript end sites (TES) of public long-read RNA sequencing (LR-RNA-seq) data. Notably, ∼10%–20% of LR-RNA-seq TES do not match our annotated PAS, suggesting 3′ end artifacts derived plausibly from internal A-rich regions of RNA. However, LR-RNA-seq data substantially complement RefSeq-based assignment of PAS to genes and are highly valuable in subtyping APA events in the context of splicing configuration. PolyADB v4 also contains PAS conservation and PAS strength information and is linked to UCSC Genome Browser for data visualization.
Yu et al. (Tue,) studied this question.