The DOI matches its Crossref record; 59 of the 62 references it cites were found in a registry or an index.
Widespread Shortening of 3′UTRs by Alternative Cleavage and Polyadenylation Activates Oncogenes in Cancer Cells
Open accessAbstract
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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“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]
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“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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Metadata
- 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)
- PMC
- PMC2819821
- 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
- bronze
- doi.org
- Licence
- 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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