The implications of structured 5′ untranslated regions on translation and disease
Abstract
Translational control is a key step in eukaryotic gene expression. The majority of translational control occurs at the level of initiation, thus implicating the 5' untranslated region as a major site of translational regulation. Many growth-related mRNAs have atypical 5' UTRs, which are often long and GC-rich. Such features promote formation of stable secondary structure, and many mRNAs encoding proteins involved in cell growth, proliferation and apoptosis have structured 5' UTRs, which in many cases harbour internal ribosome entry sites (IRESs) and upstream open-reading frames (uORFs). In this review we discuss how secondary structural elements in the 5' UTR can regulate translation and how mutations that perturb these secondary structural elements can have implications for disease and tumourigenesis.
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A hairpin situated not far from a cap with a free energy of −30 to 50 kcal/mol may be sufficient to block access of the 43S preinitiation complex and inhibit translation.
“A hairpin situated not far from a cap with a free energy of −30 to 50 kcal/mol may be sufficient for blocking the access of the 43S preinitiation complex (which scans the 5′UTR to reach the start codon) and for inhibition of translation [47,48].”
From Effects of Combinations of Untranslated-Region Sequences on Translation of mRNA (2023) · cites this paper as [48]
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Smedley, D., Schubach, M., Jacobsen, J. O. B., Köhler, S., Zemojtel, T., Spielmann, M., Jäger, M., Hochheiser, H., Washington, N. L., McMurry, J. A., et al. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2016.07.005 · Cited by 283 · see citing works
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Improved translation efficiency of injected mRNA during early embryonic development
Fink, M., Flekna, G., Ludwig, A., Heimbucher, T., & Czerny, T. (2006) · Developmental Dynamics · doi:10.1002/dvdy.20995 · Cited by 40 · see citing works
Effects of Combinations of Untranslated-Region Sequences on Translation of mRNA
Kirshina, A., Vasileva, O., Kunyk, D., Seregina, K., Muslimov, A., Ivanov, R., & Reshetnikov, V. (2023) · Biomolecules · doi:10.3390/biom13111677 · Cited by 26 · see citing works
- Authors
- Pickering, B. M., & Willis, A. E.
- Affiliations
- University of Leicester (GB)
- Southampton General Hospital (GB)
- Corresponding author
- Willis, Anne E
- ORCID
- Willis, Anne E
- Venue
- Seminars in Cell & Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2005-02
- Volume
- 16
- Issue
- 1
- Pages
- 39-47
- ISSN
- 1084-9521 (ISSN-L)
- OpenAlex
- W2081224211
- Cited by
- 339
- References
- 1
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 10 · 2022: 8 · 2021: 6 · 2020: 6 · 2019: 14 · 2018: 14 · 2017: 13 · 2016: 11 · 2015: 16 · 2014: 21 · 2013: 20 · 2012: 34
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Seminars in Cell and Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion)
- Funders
- Biotechnology and Biological Sciences Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Keywords
- 5' untranslated region, mRNA secondary structure, translational regulation, translation initiation, internal ribosome entry site, upstream open reading frames, tumourigenesis, pathogenic variants, cell proliferation, apoptosis
- MeSH terms
- Nucleic Acid Conformation, RNA, Protein Biosynthesis, 5' Untranslated Regions, Genetic Diseases, Inborn
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