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Cited by 1,179RNA Research and SplicingRNA regulation and diseaseCancer-related molecular mechanisms research

Alternative polyadenylation of mRNA precursors

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Tian, Bin, Manley, James L.·2017·Nature Reviews Molecular Cell Biology
DOI 10.1038/nrm.2016.116PMC PMC5483950
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Abstract

Alternative polyadenylation (APA) is an RNA-processing mechanism that generates distinct 3' termini on mRNAs and other RNA polymerase II transcripts. It is widespread across all eukaryotic species and is recognized as a major mechanism of gene regulation. APA exhibits tissue specificity and is important for cell proliferation and differentiation. In this Review, we discuss the roles of APA in diverse cellular processes, including mRNA metabolism, protein diversification and protein localization, and more generally in gene regulation. We also discuss the molecular mechanisms underlying APA, such as variation in the concentration of core processing factors and RNA-binding proteins, as well as transcription-based regulation.

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  • The 3′ UTR harbors polyadenylation signals, which can generate multiple isoforms with distinct 3′ ends through alternative polyadenylation.

    “The 3′ untranslated region (UTR) harbors regulatory regions called polyadenylation signals (PASs), which can generate multiple isoforms with distinct 3′ ends through alternative polyadenylation (APA)39–41.”

    From Predicting RNA-seq coverage from DNA sequence as a unifying model of gene regulation (2025) · cites this paper as [40]

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Authors
Tian, B., & Manley, J. L.
Affiliations
  • Rutgers, The State University of New Jersey (US)
  • Columbia University (US)
Corresponding author
  • Tian, Bin
  • Manley, James L.
ORCID
Venue
Nature Reviews Molecular Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2016-09-28
Volume
18
Issue
1
Pages
18-30
ISSN
  • 1471-0072 (ISSN-L)
  • 1471-0080
DOI
10.1038/nrm.2016.116
PMC
PMC5483950
OpenAlex
W2525507785
Cited by
1,179
References
178
Citations by year
2026: 117 · 2025: 126 · 2024: 155 · 2023: 117 · 2022: 145 · 2021: 163 · 2020: 123 · 2019: 105 · 2018: 75 · 2017: 52 · 2012: 1
FWCI
7.01
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Reviews Molecular Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of General Medical Sciences (R01GM028983, R01GM084089, R35GM118136)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords
alternative polyadenylation, mRNA 3' end, cleavage and polyadenylation factor, RNA-binding proteins, splicing, transcriptional regulation, mRNA metabolism, protein diversification, protein localization, gene expression regulation, cell proliferation, cell differentiation, tissue specificity
MeSH terms
Exons, Gene Expression Regulation, Humans, RNA Precursors, RNA, Messenger, RNA-Binding Proteins, Ribonucleoprotein, U1 Small Nuclear, 3' Untranslated Regions, RNA Stability, Active Transport, Cell Nucleus, Polyadenylation

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