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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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Cites
MicroRNAs: Target Recognition and Regulatory Functions
Bartel, D. P. (2009) · Cell · doi:10.1016/j.cell.2009.01.002 · Cited by 20,068
Self-citationThe C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14
Lee, R. C., Feinbaum, R. L., & Ambros, V. (1993) · Cell · doi:10.1016/0092-8674(93)90529-y · Cited by 12,948
Lewis, B. P., Burge, C. B., & Bartel, D. P. (2005) · Cell · doi:10.1016/j.cell.2004.12.035 · Cited by 11,855
Self-citation(2008) · doi:10.1038/nrg2290 · Cited by 5,199
Alternative isoform regulation in human tissue transcriptomes
Wang, E. T., Sandberg, R., Luo, S., Khrebtukova, I., Zhang, L., Mayr, C., Kingsmore, S. F., Schroth, G. P., & Burge, C. B. (2008) · Nature · doi:10.1038/nature07509 · Cited by 5,181
Self-citationCalin, G. A., Dumitru, C. D., Shimizu, M., Bichi, R., Zupo, S., Noch, E., Aldler, H., Rattan, S., Keating, M., Rai, K., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.242606799 · Cited by 5,111
Wightman, B., Ha, I., & Ruvkun, G. (1993) · Cell · doi:10.1016/0092-8674(93)90530-4 · Cited by 4,292
MicroRNA Targeting Specificity in Mammals: Determinants beyond Seed Pairing
Grimson, A., Farh, K. K.-H., Johnston, W. K., Garrett-Engele, P., Lim, L. P., & Bartel, D. P. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.06.017 · Cited by 3,766
Self-citationRAS Is Regulated by the let-7 MicroRNA Family
Johnson, S., Großhans, H., Shingara, J., Byrom, M., JARVIS, R., Cheng, A., Labourier, E., Reinert, K. L., Brown, D., & Slack, F. J. (2005) · Cell · doi:10.1016/j.cell.2005.01.014 · Cited by 3,699
A microRNA polycistron as a potential human oncogene
He, L., Thomson, J. M., Hemann, M. T., Hernando, E., Mu, D., Goodson, S. G., Powers, S., Cordon‐Cardo, C., Lowe, S. W., Hannon, G. J., et al. (2005) · Nature · doi:10.1038/nature03552 · Cited by 3,642
AU-rich elements: characterization and importance in mRNA degradation
Chen, C.-Y. A., & Shyu, A.-B. (1995) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)89102-1 · Cited by 1,948
let-7 Regulates Self Renewal and Tumorigenicity of Breast Cancer Cells
Yu, F., Yao, H., Zhu, P., Zhang, X., Pan, Q., Gong, C., Huang, Y., Hu, X., Su, F., Lieberman, J., et al. (2007) · Cell · doi:10.1016/j.cell.2007.10.054 · Cited by 1,906
Molecular themes in oncogenesis
Bishop, J. M. (1991) · Cell · doi:10.1016/0092-8674(91)90636-d · Cited by 1,629
Sandberg, R., Neilson, J. R., Sarma, A., Sharp, P. A., & Burge, C. B. (2008) · Science · doi:10.1126/science.1155390 · Cited by 1,349
The tumor suppressor microRNA let-7 represses the HMGA2 oncogenePreprint
Lee, Y. S., & Dutta, A. (2007) · Genes & Development · doi:10.1101/gad.1540407 · Cited by 1,155
Disrupting the Pairing Between let-7 and Hmga2 Enhances Oncogenic Transformation
Mayr, C., Hemann, M. T., & Bartel, D. P. (2007) · Science · doi:10.1126/science.1137999 · Cited by 1,112
Self-citationFrom Birth to Death: The Complex Lives of Eukaryotic mRNAs
Moore, M. J. (2005) · Science · doi:10.1126/science.1111443 · Cited by 1,035
A large-scale analysis of mRNA polyadenylation of human and mouse genes
Tian, B. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki158 · Cited by 970
Rosenwald, A., Wright, G. W., Wiestner, A. U., Chan, W. C., Connors, J. M., Campo, E., Gascoyne, R. D., Grogan, T. M., Müller-Hermelink, H. K., Smeland, E. B., et al. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00028-x · Cited by 913
Mechanism and regulation of mRNA polyadenylation
Colgan, D. F., & Manley, J. L. (1997) · Genes & Development · doi:10.1101/gad.11.21.2755 · Cited by 784
Early origins and evolution of microRNAs and Piwi-interacting RNAs in animals
Grimson, A., Srivastava, M., Fahey, B., Woodcroft, B. J., Chiang, H. R., King, N., Degnan, B. M., Rokhsar, D. S., & Bartel, D. P. (2008) · Nature · doi:10.1038/nature07415 · Cited by 756
Self-citationOta, A., Tagawa, H., Karnan, S., Tsuzuki, S., Karpas, A., Kira, S., Yoshida, Y., & Seto, M. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3773 · Cited by 736
Nielsen, J., Christiansen, J., Lykke-Andersen, J., Johnsen, A. H., Wewer, U. M., & Nielsen, F. C. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.2.1262 · Cited by 721
Ji, Z., Lee, J. Y., Pan, Z., Jiang, B., & Tian, B. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900028106 · Cited by 609
Characterization of a β-Actin mRNA Zipcode-Binding Protein
Ross, A. F., Oleynikov, Y., Kislauskis, E., Taneja, K. L., & Singer, R. H. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.4.2158 · Cited by 563
Molecular Architecture of the Human Pre-mRNA 3′ Processing Complex
Shi, Y., Giammartino, D. C. D., Taylor, D. J., Sarkeshik, A., Rice, W. J., Yates, J. R., Frank, J., & Manley, J. L. (2009) · Molecular Cell · doi:10.1016/j.molcel.2008.12.028 · Cited by 560
Alternative poly(A) site selection in complex transcription units: means to an end?
Edwalds-Gilbert, G. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.13.2547 · Cited by 509
Hoeflich, K. P., O'Brien, C. L., Boyd, Z. S., Cavet, G., Guerrero, S., Jung, K., Januario, T., Savage, H. M., Punnoose, E. A., Truong, T., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-0317 · Cited by 474
Flavell, S. W., Kim, T.-K., Gray, J. M., Harmin, D. A., Hemberg, M., Hong, E. J., Markenscoff-Papadimitriou, E., Bear, D. M., & Greenberg, M. E. (2008) · Neuron · doi:10.1016/j.neuron.2008.11.029 · Cited by 440
Proudfoot, N. J. (1991) · Cell · doi:10.1016/0092-8674(91)90495-k · Cited by 432
Takagaki, Y., Seipelt-Thiemann, R. L., Peterson, M. L., & Manley, J. L. (1996) · Cell · doi:10.1016/s0092-8674(00)82000-0 · Cited by 425
Deregulated c-fos expression interferes with normal bone development in transgenic mice
Rüther, U., Garber, C., Komitowski, D. D., Müller, R., & Wagner, E. F. (1987) · Nature · doi:10.1038/325412a0 · Cited by 332
The Guardian's Little Helper: MicroRNAs in the p53 Tumor Suppressor Network
He, X., He, L., & Hannon, G. J. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-2672 · Cited by 319
Chromosome translocations: dangerous liaisons revisited
Rowley, J. D. (2001) · Nature reviews. Cancer · doi:10.1038/35106108 · Cited by 271
Wiestner, A. U., Tehrani, M., Chiorazzi, M., Wright, G. W., Gibellini, F., Nakayama, K., Liu, H., Rosenwald, A., Müller‐Hermelink, H. K., Ott, G., et al. (2007) · Blood · doi:10.1182/blood-2006-08-039859 · Cited by 259
Conserved GU-Rich Elements Mediate mRNA Decay by Binding to CUG-Binding Protein 1
Louis, I. V.-S., Tahoe, N. M., Fan, D., Larsson, O. S., Rattenbacher, B., SternJohn, J. R., Vasdewani, J., Karypis, G., Reilly, C., Bitterman, P. B., et al. (2008) · Molecular Cell · doi:10.1016/j.molcel.2007.11.024 · Cited by 248
CRD-BP mediates stabilization of βTrCP1 and c-myc mRNA in response to β-catenin signalling
Noubissi, F. K., Elcheva, I. A., Bhatia, N., Shakoori, A., Ougolkov, A. V., Liu, J., Minamoto, T., Ross, J., Fuchs, S. Y., & Spiegelman, V. S. (2006) · Nature · doi:10.1038/nature04839 · Cited by 244
Promoter usage and alternative splicing
Kornblihtt, A. R. (2005) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.04.014 · Cited by 236
Overexpression of the HMGA2 gene in transgenic mice leads to the onset of pituitary adenomas
Fedele, M., Battista, S., Kenyon, L. C., Baldassarre, G., Fidanza, V., Klein–Szanto, A. J., Parlow, A. F., Visone, R., Pierantoni, G. M., Outwater, E. K., et al. (2002) · Oncogene · doi:10.1038/sj.onc.1205428 · Cited by 214
Evron, E., Umbricht, C. B., Korz, D., Raman, V., Loeb, D. M., Niranjan, B., Buluwela, L., Weitzman, S. A., Marks, J. R., & Sukumar, S. V. (2001) · PubMed · Cited by 212
An interaction between U2AF 65 and CF Im links the splicing and 3′ end processing machineries
Millevoi, S., Loulergue, C., Dettwiler, S., Karaa, Z. S., Keller, W., Antoniou, M. N., & Vagner, S. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601331 · Cited by 203
Translation factors promote the formation of two states of the closed-loop mRNP
Amrani, N., Ghosh, S., Mangus, D. A., & Jacobson, A. (2008) · Nature · doi:10.1038/nature06974 · Cited by 200
Doyle, G. A. R., Leeds, P., Fleisig, A. J., Ross, J., Betz, N. A., & Prokipcak, R. D. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.22.5036 · Cited by 176
Vagner, S., Vagner, C., & Mattaj, I. W. (2000) · Genes & Development · doi:10.1101/gad.14.4.403 · Cited by 172
Alternative Polyadenylation: A Twist on mRNA 3′ End Formation
Lutz, C. S. (2008) · ACS Chemical Biology · doi:10.1021/cb800138w · Cited by 160
Lou, H. J., Helfman, D. M., Gagel, R. F., & Berget, S. M. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.1.78 · Cited by 149
Veraldi, K. L., Arhin, G. K., Martincic, K., Chung-Ganster, L.-H., Wilusz, J., & Milcarek, C. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.4.1228-1238.2001 · Cited by 143
Spatial preferences of microRNA targets in 3' untranslated regions
Majoros, W. H., & Ohler, U. (2007) · BMC Genomics · doi:10.1186/1471-2164-8-152 · Cited by 128
Lukáš, J., Bártková, J., Welcker, M., PETERSEN, O. W., Peters, G., Strauss, M., & Bartek, J. J. (1995) · PubMed · Cited by 115
Mammary Tumor Induction in Transgenic Mice Expressing an RNA-Binding Protein
Tessier, C. R., Doyle, G. A. R., Clark, B. A., Pitot, H. C., & Ross, J. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-2927 · Cited by 110
Hall‐Pogar, T., Liang, S., Hague, L. K., & Lutz, C. S. (2007) · RNA · doi:10.1261/rna.577707 · Cited by 93
Principles of Gene Manipulation and Genomics
Primrose, S. B., & Twyman, R. M. (2002) · Cited by 88
Martincic, K., Campbell, R. L., Edwalds-Gilbert, G., Souan, L., Lotze, M. T., & Milcarek, C. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.19.11095 · Cited by 85
A truncated cyclin D1 gene encodes a stable mRNA in a human breast cancer cell line.
Lebwohl, D., Muise‐Helmericks, R. C., Sepp‐Lorenzino, L., Serve, S., Timaul, M. N., Bol, R., Borgen, P. I., & Rosen, N. X. (1994) · PubMed · Cited by 84
Terminal riboadenylate transferase in human lymphocytes
Colemán, M. S., Hutton, J. J., & Bollum, F. J. (1974) · Nature · doi:10.1038/248407a0 · Cited by 57
Miyamoto, S., Chiorini, J. A., Urcelay, E., & Safer, B. (1996) · Biochemical Journal · doi:10.1042/bj3150791 · Cited by 55
Increased rate of RNA-polyadenylation
Häuser, H., Knippers, R., & Schäfer, K. (1978) · Experimental Cell Research · doi:10.1016/0014-4827(78)90247-1 · Cited by 25
Separation of RNA According to Size: Electrophoresis of Glyoxylated RNA through Agarose GelsPreprint
Sambrook, J., & Russell, D. W. (2006) · Cold Spring Harbor Protocols · doi:10.1101/pdb.prot4057 · Cited by 10
Derynck, R., & Wagner, E. F. (1995) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(95)80068-9 · Cited by 9
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Agarwal, V., Bell, G. W., Nam, J.-W., & Bartel, D. P. (2015) · eLife · doi:10.7554/elife.05005 · Cited by 7,318
Self-citationA ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language?
Salmena, L., Poliseno, L., Tay, Y., Kats, L., & Pandolfi, P. P. (2011) · Cell · doi:10.1016/j.cell.2011.07.014 · Cited by 7,262
U1 snRNP regulates cancer cell migration and invasion in vitro
Oh, J.-M., Venters, C. C., Di, C., Pinto, A. M., Wan, L., Younis, I., Cai, Z., Arai, C., So, B. R., Duan, J., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-13993-7 · Cited by 7,157
The widespread regulation of microRNA biogenesis, function and decay
Krol, J., Loedige, I., & Filipowicz, W. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2843 · Cited by 4,672
Insights into the regulation of protein abundance from proteomic and transcriptomic analyses
Vogel, C., & Marcotte, E. M. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3185 · Cited by 4,195
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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