Features in the 5′ non-coding sequences of rabbit α and β-globin mRNAs that affect translational efficiency
Abstract
The 5' non-coding sequence of rabbit beta-globin mRNA was mutagenized in an attempt to identify structural features that might contribute to the ability to support translation in an homologous rabbit reticulocyte lysate. Translational efficiency was not reduced by substitutions introduced in nearly every position of the beta-globin leader sequence, suggesting that the 5' non-coding domain of this highly efficient mRNA contains no special effector motifs. Instead, efficient translation appears to require only a moderately long leader sequence devoid of secondary structure, especially near the 5' end. Consistent with that interpretation, substitutions in several positions actually improved translation relative to the wild-type beta-globin leader sequence; experimental assessment of the secondary structure of these derivatives revealed a perfect inverse correlation between secondary structure content and translational efficiency. Other experiments probed the structural basis for the long-noted difference in translational efficiency between rabbit alpha and beta-globin mRNAs, a difference that was reproduced here using only the 5' non-coding domains of those mRNAs. The possibility that translation of ribosomal protein mRNAs might be modulated by a mechanism similar to that of alpha-globin mRNA is discussed. Because the beta-globin leader sequence has been incorporated into some popular expression vectors, and because globin genes are targets for gene therapy, this analysis of how…
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Globin gene sequences are often used to ensure high translation efficiency.
“Globin gene sequences are often used to ensure high translation efficiency.”
From Untranslated Region Sequences and the Efficacy of mRNA Vaccines against Tuberculosis (2024) · cites this paper as [10]
The 5′UTR of rabbit β-globin mRNA is thought to mediate efficient cap-dependent translation and does not contain secondary structures or sequence elements that may negatively affect translation.
“The 5′UTR of rabbit β-globin mRNA is thought to mediate efficient cap-dependent translation and does not contain any secondary structures or sequence elements that may negatively affect translation [10].”
From Untranslated Region Sequences and the Efficacy of mRNA Vaccines against Tuberculosis (2024) · cites this paper as [10]
Sequences of human or rabbit α- and β-globin or of rabbit β-globin have been used to improve translational efficiency of heterologous mRNAs.
“In particular, sequences of human or rabbit α- and β-globin or of rabbit β-globin have been used to improve translational efficiency of heterologous mRNAs [36,37,38].”
From Effects of Combinations of Untranslated-Region Sequences on Translation of mRNA (2023) · cites this paper as [37]
The 5′UTR of rabbit β-globin (Rabb) consists of 52 nucleotides and does not contain strong secondary structures.
“In contrast, the 5′UTR of rabbit β-globin (Rabb) consists of 52 nucleotides and does not contain strong secondary structures [37].”
From Effects of Combinations of Untranslated-Region Sequences on Translation of mRNA (2023) · cites this paper as [37]
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Improved translation efficiency of therapeutic mRNA
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Untranslated Region Sequences and the Efficacy of mRNA Vaccines against Tuberculosis
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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
- Kozak, M.
- Affiliations
- University of Medicine and Dentistry of New Jersey (US)
- Corresponding author
- Kozak, Marilyn
- Venue
- Journal of Molecular Biology
- Publisher
- Elsevier BV
- Published
- 1994-01
- Volume
- 235
- Issue
- 1
- Pages
- 95-110
- ISSN
- 0022-2836 (ISSN-L)
- OpenAlex
- W2006776507
- Cited by
- 101
- References
- 0
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 1 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 3 · 2014: 3 · 2013: 2 · 2012: 2
- FWCI
- 2.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM 33915, R01GM033915)
- 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
- mRNA leader sequence, translation efficiency, beta-globin mRNA, alpha-globin mRNA, mRNA secondary structure, rabbit reticulocyte lysate, ribosomal protein mRNAs, mutagenesis, gene therapy vectors, globin genes
- MeSH terms
- Animals, Base Sequence, Globins, Methionine, Molecular Sequence Data, Nucleic Acid Conformation, Oligodeoxyribonucleotides, Rabbits, RNA, Messenger, Transcription, Genetic, Protein Biosynthesis, Xenopus, Restriction Mapping, Mutagenesis, Site-Directed, Protein Structure, Secondary, Protein Sorting Signals
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