Cited by 196RNA Research and SplicingGenomics and Phylogenetic StudiesRNA regulation and disease

PolyASite 2.0: a consolidated atlas of polyadenylation sites from 3′ end sequencing

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Herrmann, Christina J, Schmidt, Ralf, Kanitz, Alexander, Artimo, Panu, Gruber, Andreas J, Zavolan, Mihaela·2019·Nucleic Acids Research

Abstract

Generated by 3' end cleavage and polyadenylation at alternative polyadenylation (poly(A)) sites, alternative terminal exons account for much of the variation between human transcript isoforms. More than a dozen protocols have been developed so far for capturing and sequencing RNA 3' ends from a variety of cell types and species. In previous studies, we have used these data to uncover novel regulatory signals and cell type-specific isoforms. Here we present an update of the PolyASite (https://polyasite.unibas.ch) resource of poly(A) sites, constructed from publicly available human, mouse and worm 3' end sequencing datasets by enforcing uniform quality measures, including the flagging of putative internal priming sites. Through integrated processing of all data, we identified and clustered sites that are closely spaced and share polyadenylation signals, as these are likely the result of stochastic variations in processing. For each cluster, we identified the representative - most frequently processed - site and estimated the relative use in the transcriptome across all samples. We have established a modern web portal for efficient finding, exploration and export of data. Database generation is fully automated, greatly facilitating incorporation of new datasets and the updating of underlying genome resources.

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  • To reduce the risk of picking genes in which the perceived APA is driven by 3′ bias in GTEx RNA-seq data, the authors required that the genes also exhibited differential distal polyadenylation in cell-type-matched experiments from the PolyASite 2.0 database.

    “To reduce the risk of picking genes in which the perceived APA is driven by 3′ bias in the GTEx RNA-seq data, we required that the genes also exhibited differential distal polyadenylation in cell-type-matched experiments from the PolyASite 2.0 database42.”
  • RWDD1 exhibits biased usage of the distal-most polyadenylation site in brain.

    “For example, RWDD1 exhibits biased usage of the distal-most PAS in brain42 (Fig. 2e; see Extended Data Fig. 3b for additional examples).”

    From Predicting RNA-seq coverage from DNA sequence as a unifying model of gene regulation (2025) · cites this paper as [42]

    The Introduction describes PolyASite’s per-sample poly(A)-site usage data, but does not report a result for RWDD1 in brain. Searches for “RWDD1,” “brain,” and distal-site usage found no passage in our copy addressing the claimed bias. (LLM, conf=0.76)

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Authors
Herrmann, C. J., Schmidt, R., Kanitz, A., Artimo, P., Gruber, A. J., & Zavolan, M.
Affiliations
  • University of Basel (CH)
  • SIB Swiss Institute of Bioinformatics (CH)
  • University of Oxford (GB)
Corresponding author
Zavolan, Mihaela
Venue
Nucleic Acids Research
Published
2019-10-16
Volume
48
Issue
D1
Pages
D174-D179
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
OpenAlex
W2980708325
Cited by
196
References
32
Citations by year
2026: 18 · 2025: 21 · 2024: 33 · 2023: 36 · 2022: 37 · 2021: 40 · 2020: 10 · 2019: 1
FWCI
7.28
Type
journal article
Language
en
Open access
Locations
  • Nucleic Acids Research (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • KOPS (University of Konstanz) (submittedVersion, cc-by-nc)
  • edoc (University of Basel) (submittedVersion)
Funders
Swiss National Science Foundation (31003A_170216, 51NF40_141735)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords
polyadenylation sites, alternative polyadenylation, 3' end sequencing, mRNA isoforms, site clustering, web portal
MeSH terms
Animals, Humans, Poly A, Caenorhabditis elegans, Sequence Analysis, RNA, Polyadenylation, Databases, Nucleic Acid, Mice

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