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PolyA_DB v4: systematic polyA site identification and isoform annotation in human and mouse genomes using 3' end and
Shan Yu1, Wei Chun Chen1, Luyang Wang1
1Genome Regulation and Cell Signalling Program, Ellen and Ronald Caplan Cancer Center, The Wistar Institute, Philadelphia, PA 19104, United States.
Nucleic Acids Research
|November 29, 2025
Summary
PolyA_DB version 4 significantly expands the database of cleavage and polyadenylation sites (PAS) in mammalian genomes. This update enhances our understanding of alternative polyadenylation (APA) by identifying millions of new PAS and validating them with long-read RNA sequencing data.
Area of Science:
- Genomics
- Molecular Biology
- Bioinformatics
Background:
- The 3' end of eukaryotic RNAs is defined by cleavage and polyadenylation sites (PAS).
- Alternative polyadenylation (APA) leads to diverse RNA isoforms from single genes.
- Accurate annotation of PAS is crucial for understanding RNA biology.
Purpose of the Study:
- To present PolyA_DB version 4, an updated database of mammalian cleavage and polyadenylation sites (PAS).
- To enhance the coverage and accuracy of PAS annotation in human and mouse genomes.
- To integrate and analyze long-read RNA sequencing data for PAS validation and APA event subtyping.
Main Methods:
- Exhaustive mining of human and mouse transcriptomic data using the 3' region extraction and deep sequencing plus (3'READS+) method.
- Identification and annotation of approximately 1.4 million PAS in human and mouse genomes.
- Comparison and integration of identified PAS with long-read RNA sequencing (LR-RNA-seq) transcript end sites (TES).
Main Results:
- PolyA_DB v4 identifies ∼1.4 million PAS in human and mouse genomes, a significant increase in coverage.
- 20% of the full PAS set (Max collection) aligns with LR-RNA-seq TES.
- LR-RNA-seq data complements RefSeq-based PAS assignment and aids in subtyping APA events.
Conclusions:
- PolyA_DB v4 provides a comprehensive resource for mammalian PAS, greatly improving coverage and accuracy.
- LR-RNA-seq data is valuable for validating PAS and characterizing APA events, though potential artifacts require careful consideration.
- The updated database facilitates research into RNA processing, gene regulation, and the functional impact of APA isoforms.
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