Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (659 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
The addition of a tail of polyadenylic acid (POLY A) to the 3' end of mRNA (RNA, messenger). Polyadenylation involves recognizing the processing site signal, (aauaaa), and cleaving of the mRNA to create a 3' OH terminal end to which poly A polymerase (polynucleotide adenylyltransferase) adds 60-200 adenylate residues. The 3' end processing of some messenger RNAs, such as histone mRNA, is carried out by a different process that does not include the addition of poly A as described here.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Polyadenylations.
Where it fits in the MeSH classification
- Broader topics
- RNA 3' End Processing
Related concepts
- Messenger
- Aauaaa
- Polynucleotide Adenylyltransferase
Research landscape
PubMed indexes 2,554 records tagged with the MeSH heading “Polyadenylation” (counts retrieved 2026-10-29). 786 of them (30.8%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 1,137 records.
Reviews account for 312 records (12.2%) and meta-analyses for 4. Randomized controlled trials number 1 (0.0%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 0 |
| 2000-2009 | 649 |
| 2010-2019 | 1,137 |
| 2020 onward | 786 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 312 | 12.2% |
| Meta-analyses | 4 | 0.2% |
| Randomized controlled trials | 1 | 0.0% |
Method: PubMed query "Polyadenylation"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in molecular biology
Molecular biology establishes mechanisms through controlled experiments, often in simplified systems such as purified proteins, cultured cells or model organisms. Such work can show what is possible in a defined system, but whether a pathway matters in a whole organism or in human disease needs further evidence. Check the experimental system, whether findings were reproduced by independent groups, and whether the authors tested the mechanism directly or inferred it from correlation.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Heteromeric RNP Assembly at LINEs Controls Lineage-Specific RNA Processing | 2018 | Research article Design not recorded in structured metadata | 150 | cc by PMID 30078707 · DOI · PMC6108849 |
| Alternative polyadenylation: methods, mechanism, function, and role in cancer | 2021 | Review article Design not recorded in structured metadata | 133 | cc by PMID 33526057 · DOI · PMC7852185 |
| The role of alternative polyadenylation in the antiviral innate immune response | 2017 | Research article Design not recorded in structured metadata | 111 | cc by PMID 28233779 · DOI · PMC5333124 |
| NUDT21-mediated Alternative Polyadenylation of CDK19 Reprograms Cholesterol Biosynthesis to Drive Colorectal Cancer Progression | 2026 | Research article Design not recorded in structured metadata | 6 | cc by PMID 41255211 · DOI · PMC12866688 |
Heteromeric RNP Assembly at LINEs Controls Lineage-Specific RNA Processing [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Long mammalian introns make it challenging for the RNA processing machinery to identify exons accurately.
- Closing excerpt
- VIDEO ABSTRACT.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (152 words)
Long mammalian introns make it challenging for the RNA processing machinery to identify exons accurately. We find that LINE-derived sequences (LINEs) contribute to this selection by recruiting dozens of RNA-binding proteins (RBPs) to introns. This includes MATR3, which promotes binding of PTBP1 to multivalent binding sites within LINEs. Both RBPs repress splicing and 3' end processing within and around LINEs. Notably, repressive RBPs preferentially bind to evolutionarily young LINEs, which are located far from exons. These RBPs insulate the LINEs and the surrounding intronic regions from RNA processing. Upon evolutionary divergence, changes in RNA motifs within LINEs lead to gradual loss of their insulation. Hence, older LINEs are located closer to exons, are a common source of tissue-specific exons, and increasingly bind to RBPs that enhance RNA processing. Thus, LINEs are hubs for the assembly of repressive RBPs and also contribute to the evolution of new, lineage-specific transcripts in mammals. VIDEO ABSTRACT.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 30078707 · DOI · PMC6108849
Alternative polyadenylation: methods, mechanism, function, and role in cancer [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Occurring in over 60% of human genes, alternative polyadenylation (APA) results in numerous transcripts with differing 3'ends, thus greatly expanding the diversity of mRNAs and of proteins derived from a single gene.
- Closing excerpt
- Finally, we summarize the current understanding of APA in cancer and provide our vision for future APA related research.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (176 words)
Occurring in over 60% of human genes, alternative polyadenylation (APA) results in numerous transcripts with differing 3'ends, thus greatly expanding the diversity of mRNAs and of proteins derived from a single gene. As a key molecular mechanism, APA is involved in various gene regulation steps including mRNA maturation, mRNA stability, cellular RNA decay, and protein diversification. APA is frequently dysregulated in cancers leading to changes in oncogenes and tumor suppressor gene expressions. Recent studies have revealed various APA regulatory mechanisms that promote the development and progression of a number of human diseases, including cancer. Here, we provide an overview of four types of APA and their impacts on gene regulation. We focus particularly on the interaction of APA with microRNAs, RNA binding proteins and other related factors, the core pre-mRNA 3'end processing complex, and 3'UTR length change. We also describe next-generation sequencing methods and computational tools for use in poly(A) signal detection and APA repositories and databases. Finally, we summarize the current understanding of APA in cancer and provide our vision for future APA related research.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 33526057 · DOI · PMC7852185
The role of alternative polyadenylation in the antiviral innate immune response [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Alternative polyadenylation (APA) is an important regulatory mechanism of gene functions in many biological processes.
- Closing excerpt
- Thus, our study reports the annotation of genes with APA in antiviral immunity and highlights the roles of 3' processing factors on 3' UTR variation upon viral infection.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (135 words)
Alternative polyadenylation (APA) is an important regulatory mechanism of gene functions in many biological processes. However, the extent of 3' UTR variation and the function of APA during the innate antiviral immune response are unclear. Here, we show genome-wide poly(A) sites switch and average 3' UTR length shortens gradually in response to vesicular stomatitis virus (VSV) infection in macrophages. Genes with APA and mRNA abundance change are enriched in immune-related categories such as the Toll-like receptor, RIG-I-like receptor, JAK-STAT and apoptosis-related signalling pathways. The expression of 3' processing factors is down-regulated upon VSV infection. When the core 3' processing factors are knocked down, viral replication is affected. Thus, our study reports the annotation of genes with APA in antiviral immunity and highlights the roles of 3' processing factors on 3' UTR variation upon viral infection.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 28233779 · DOI · PMC5333124
NUDT21-mediated Alternative Polyadenylation of CDK19 Reprograms Cholesterol Biosynthesis to Drive Colorectal Cancer Progression [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Alternative polyadenylation (APA) is critical for shaping transcriptome diversity by generating mRNA isoforms that differ in the length of their 3'untranslated region (3'UTR).
- Closing excerpt
- The findings establish the NUDT21-CDK19 axis as a central hub integrating APA manner, cholesterol metabolic reprogramming, and immune evasion in CRC, unveiling potential therapeutic opportunities.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (196 words)
Alternative polyadenylation (APA) is critical for shaping transcriptome diversity by generating mRNA isoforms that differ in the length of their 3'untranslated region (3'UTR). APA dysregulation, a defined feature of tumorigenesis, remains poorly understood in colorectal cancer (CRC). Here, CRISPR/Cas9 screening identifies APA regulator NUDT21 as a key driver of CRC progression. NUDT21 is overexpressed in CRC tumors and correlates with poor prognosis in CRC patients. Genetic ablation of NUDT21 impairs CRC cell proliferation and triggers CD8+ T cell anti-tumor response through disrupting cholesterol biosynthesis, leading to delayed tumor progression in syngeneic mouse models. Mechanistically, NUDT21 promotes the generation of cyclin-dependent kinase 19 (CDK19) mRNA isoforms with long 3'UTR by directing usage of distal polyadenylation sites. The long 3'UTR facilitates the export of CDK19 transcripts to the cytoplasm and supports their efficient translation, with no impact on their stability. Truncation of the long 3'UTR of Cdk19 recapitulates cholesterol biosynthesis and proliferative impairments, as well as the enhanced anti-tumor CD8+ T cell activity observed upon NUDT21 depletion, whereas CDK19 overexpression rescues these phenotypes. The findings establish the NUDT21-CDK19 axis as a central hub integrating APA manner, cholesterol metabolic reprogramming, and immune evasion in CRC, unveiling potential therapeutic opportunities.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41255211 · DOI · PMC12866688
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Alternative polyadenylation of mRNA precursors [5]
- Research article Alternative cleavage and polyadenylation: extent, regulation and function [6]
- Research article Mechanisms and consequences of alternative polyadenylation [7]
- Research article Alternative cleavage and polyadenylation in health and disease [8]
- Research article Context-specific regulation and function of mRNA alternative polyadenylation [9]
- Research article Alternative polyadenylation: new insights from global analyses [10]
References
- Attig J, Agostini F, Gooding C, Chakrabarti AM, Singh A, Haberman N, et al.. Heteromeric RNP Assembly at LINEs Controls Lineage-Specific RNA Processing. . 2018. PMID 30078707 · DOI · PMC6108849
- Zhang Y, Liu L, Qiu Q, Zhou Q, Ding J, Lu Y, et al.. Alternative polyadenylation: methods, mechanism, function, and role in cancer. . 2021. PMID 33526057 · DOI · PMC7852185
- Jia X, Yuan S, Wang Y, Fu Y, Ge Y, Ge Y, et al.. The role of alternative polyadenylation in the antiviral innate immune response. . 2017. PMID 28233779 · DOI · PMC5333124
- Yu Y, Ma J, Zhou M, Gu X, Zhou Y, Li Z, et al.. NUDT21-mediated Alternative Polyadenylation of CDK19 Reprograms Cholesterol Biosynthesis to Drive Colorectal Cancer Progression. . 2026. PMID 41255211 · DOI · PMC12866688
- Tian B, Manley JL. Alternative polyadenylation of mRNA precursors. Nat Rev Mol Cell Biol. 2017. PMID 27677860 · DOI · PMC5483950
- Elkon R, Ugalde AP, Agami R. Alternative cleavage and polyadenylation: extent, regulation and function. Nat Rev Genet. 2013. PMID 23774734 · DOI
- Di Giammartino DC, Nishida K, Manley JL. Mechanisms and consequences of alternative polyadenylation. Mol Cell. 2011. PMID 21925375 · DOI · PMC3194005
- Gruber AJ, Zavolan M. Alternative cleavage and polyadenylation in health and disease. Nat Rev Genet. 2019. PMID 31267064 · DOI
- Mitschka S, Mayr C. Context-specific regulation and function of mRNA alternative polyadenylation. Nat Rev Mol Cell Biol. 2022. PMID 35798852 · DOI · PMC9261900
- Shi Y. Alternative polyadenylation: new insights from global analyses. RNA. 2012. PMID 23097429 · DOI · PMC3504663
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.