Cited by 1,613RNA Research and SplicingCancer-related molecular mechanisms researchRNA regulation and disease

Widespread Shortening of 3′UTRs by Alternative Cleavage and Polyadenylation Activates Oncogenes in Cancer Cells

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Mayr, Christine, Bartel, David P.·2009·Cell

Abstract

In cancer cells, genetic alterations can activate proto-oncogenes, thereby contributing to tumorigenesis. However, the protein products of oncogenes are sometimes overexpressed without alteration of the proto-oncogene. Helping to explain this phenomenon, we found that when compared to similarly proliferating nontransformed cell lines, cancer cell lines often expressed substantial amounts of mRNA isoforms with shorter 3' untranslated regions (UTRs). These shorter isoforms usually resulted from alternative cleavage and polyadenylation (APA). The APA had functional consequences, with the shorter mRNA isoforms exhibiting increased stability and typically producing ten-fold more protein, in part through the loss of microRNA-mediated repression. Moreover, expression of the shorter mRNA isoform of the proto-oncogene IGF2BP1/IMP-1 led to far more oncogenic transformation than did expression of the full-length, annotated mRNA. The high incidence of APA in cancer cells, with consequent loss of 3'UTR repressive elements, suggests a pervasive role for APA in oncogene activation without genetic alteration.

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Crossref · 10.1016/j.cell.2009.06.016

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  • Stem cell quiescence is controlled at least in part by mechanisms that alter 3' UTR length and thus susceptibility to miRNA regulation.

    “the importance of transcript 3′ UTRs as targets for miRNAs suggests that stem cell quiescence is controlled, at least in part, by mechanisms that alter 3′ UTR length and thus the susceptibility to regulation by miRNAs92–95.”

    From Molecular regulation of stem cell quiescence (2013) · cites this paper as [95]

  • Shortening of 3' UTRs correlates with proliferation in many cell types, including cancer cells and somatic cell reprogramming.

    “Shortening of 3′ UTRs seems to correlate with proliferation in many cell types94, including aberrant proliferation in the case of cancer cells95 or during somatic cell reprogramming99”

    From Molecular regulation of stem cell quiescence (2013) · cites this paper as [95]

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Authors
Mayr, C., & Bartel, D. P.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Memorial Sloan Kettering Cancer Center (US)
Corresponding author
  • Mayr, Christine
  • Bartel, David P.
Venue
Cell
Publisher
Elsevier BV
Published
2009-08
Volume
138
Issue
4
Pages
673-684
ISSN
0092-8674 (ISSN-L)
OpenAlex
W1542927170
Cited by
1,613
References
62
Citations by year
2026: 57 · 2025: 60 · 2024: 87 · 2023: 98 · 2022: 99 · 2021: 118 · 2020: 96 · 2019: 95 · 2018: 100 · 2017: 100 · 2016: 87 · 2015: 86 · 2014: 116 · 2013: 129 · 2012: 114
FWCI
37.94
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
  • PMC
Funders
  • Howard Hughes Medical Institute
  • National Cancer Institute (P30CA008748)
  • National Institute of General Medical Sciences (R01GM067031)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK068348)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords
alternative polyadenylation, mRNA isoforms, oncogene activation, proto-oncogenes, mRNA stability, oncogenic transformation, cancer cells
MeSH terms
Proto-Oncogene Mas, Cell Transformation, Neoplastic, Humans, Mutation, Oncogenes, Gene Expression Regulation, Neoplastic, S Phase, Cyclins, RNA-Binding Proteins, Alternative Splicing, 3' Untranslated Regions, RNA Stability, Polyadenylation, Cell Line, Tumor, Cyclin D2

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