Proliferating Cells Express mRNAs with Shortened 3' Untranslated Regions and Fewer MicroRNA Target Sites
Open accessAbstract
Messenger RNA (mRNA) stability, localization, and translation are largely determined by sequences in the 3′ untranslated region (3′UTR). We found a conserved increase in expression of mRNAs terminating at upstream polyadenylation sites after activation of primary murine CD4 + T lymphocytes. This program, resulting in shorter 3′UTRs, is a characteristic of gene expression during immune cell activation and correlates with proliferation across diverse cell types and tissues. Forced expression of full-length 3′UTRs conferred reduced protein expression. In some cases the reduction in protein expression could be reversed by deletion of predicted microRNA target sites in the variably included region. Our data indicate that gene expression is coordinately regulated, such that states of increased proliferation are associated with widespread reductions in the 3′UTR-based regulatory capacity of mRNAs.
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Cancer cell lines and proliferative cells often express transcripts with shorter 3' UTRs.
“It has recently been noted that cancer cell lines and proliferative cells often express transcripts with shorter 3Ј UTRs (51).”
From Expression of miR-33 from an SREBP2 Intron Inhibits Cholesterol Export and Fatty Acid Oxidation* (2010) · cites this paper as [51]
Longer 3′UTRs correlate with lower expression levels.
“Longer 3′UTRs correlate with lower expression levels [25].”
From Effects of Combinations of Untranslated-Region Sequences on Translation of mRNA (2023) · cites this paper as [25]
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 [94]
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 [94]
T cell activation from quiescence is associated with widespread shortening of 3' UTRs, circumventing miRNA regulation during activation.
“T cell activation from the quiescent state is associated with widespread shortening of 3′ UTRs, thereby circumventing the regulatory role of mRNA-targeting miRNAs during activation94.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [94]
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References 22 · Cited by 1,349
- Authors
- Sandberg, R., Neilson, J. R., Sarma, A., Sharp, P. A., & Burge, C. B.
- Affiliations
- Koch Institute for Integrative Cancer Research At MIT (US)
- Corresponding author
- Sandberg, Rickard
- Neilson, Joel R.
- Sharp, Phillip A.
- Burge, Christopher B.
- Venue
- Science
- Published
- 2008-06-20
- Volume
- 320
- Issue
- 5883
- Pages
- 1643-1647
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2587246
- OpenAlex
- W1964727443
- Cited by
- 1,349
- References
- 22
- Citations by year
- 2026: 43 · 2025: 43 · 2024: 45 · 2023: 76 · 2022: 69 · 2021: 84 · 2020: 64 · 2019: 63 · 2018: 72 · 2017: 84 · 2016: 63 · 2015: 77 · 2014: 98 · 2013: 117 · 2012: 104
- FWCI
- 33.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Human Genome Research Institute (R01HG002439)
- National Cancer Institute (K99CA131474, P01CA042063, P30CA014051)
- National Institute of General Medical Sciences (R01GM034277)
- National Institute of Allergy and Infectious Diseases (U19AI056900)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- 3' untranslated region, mRNA stability, microRNA binding sites, polyadenylation, cell proliferation, CD4+ T cells, immune cell activation, mRNA localization, translational regulation, gene expression regulation, protein expression
- MeSH terms
- Animals, Cell Line, Cells, Cultured, Gene Expression Regulation, Humans, Lymphocyte Activation, Mice, Inbred C57BL, RNA Splicing, RNA, Messenger, CD4-Positive T-Lymphocytes, Oligonucleotide Array Sequence Analysis, 3' Untranslated Regions, Polyadenylation, MicroRNAs, Cell Line, Tumor, Cell Proliferation, Mice
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