Multiple roles of the coding sequence 5′ end in gene expression regulation
Open accessAbstract
The codon composition of the coding sequence's (ORF) 5' end first few dozen codons is known to be distinct to that of the rest of the ORF. Various explanations for the unusual codon distribution in this region have been proposed in recent years, and include, among others, novel regulatory mechanisms of translation initiation and elongation. However, due to the fact that many overlapping regulatory signals are suggested to be associated with this relatively short region, its research is challenging. Here, we review the currently known signals that appear in this region, the theories related to the way they regulate translation and affect the organismal fitness, and the debates they provoke.
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Some studies have shown that protein expression level drops if the 5′-end leader region has more secondary structure.
“Some studies have shown that protein expression level drops if the 5′-end leader region has more secondary structure5,50–53.”
From Algorithm for optimized mRNA design improves stability and immunogenicity (2023) · cites this paper as [53]
The section “Weak mRNA Folding at the ORF’s 5′ End” reports that stronger folding near the start of the coding sequence was negatively correlated with protein levels in five studies, while noting that a sixth study did not find the correlation. The claim specifies the 5′ leader region, but the reported protein-level finding concerns the beginning of the ORF, not specifically the leader region. No page number is available in our copy. (LLM, conf=0.85)
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Self-citationLevin, D., & Tuller, T. (2020) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1008038 · Cited by 13 · see citing works
Self-citation
- Authors
- Tuller, T., & Zur, H.
- Affiliations
- Tel Aviv University (IL)
- Corresponding author
- Tuller, Tamir
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-12-12
- Volume
- 43
- Issue
- 1
- Pages
- 13-28
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC4288200
- OpenAlex
- W2046872786
- Cited by
- 206
- References
- 115
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 12 · 2023: 17 · 2022: 16 · 2021: 19 · 2020: 28 · 2019: 18 · 2018: 21 · 2017: 27 · 2016: 16 · 2015: 13 · 2014: 1
- FWCI
- 1.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nucleic Acids Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- 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 › Genomics and Chromatin Dynamics
- Keywords
- 5' untranslated region, codon usage bias, translation initiation, translation elongation, gene expression regulation, codon composition, regulatory signals, organismal fitness
- MeSH terms
- Codon, Gene Expression Regulation, Peptide Chain Initiation, Translational, Ribosomes, RNA, Messenger, RNA, Transfer, Protein Biosynthesis, Open Reading Frames, Regulatory Sequences, Ribonucleic Acid, RNA Folding
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