Translation Initiation: A Regulatory Role for Poly(A) Tracts in Front of the AUG Codon in Saccharomyces cerevisiae
Open accessAbstract
The 5′-UTR serves as the loading dock for ribosomes during translation initiation and is the key site for translation regulation. Many genes in the yeast Saccharomyces cerevisiae contain poly(A) tracts in their 5′-UTRs. We studied these pre-AUG poly(A) tracts in a set of 3274 recently identified 5′-UTRs in the yeast to characterize their effect on in vivo protein abundance, ribosomal density, and protein synthesis rate in the yeast. The protein abundance and the protein synthesis rate increase with the length of the poly(A), but exhibit a dramatic decrease when the poly(A) length is ≥12. The ribosomal density also reaches the lowest level when the poly(A) length is ≥12. This supports the hypothesis that a pre-AUG poly(A) tract can bind to translation initiation factors to enhance translation initiation, but a long (≥12) pre-AUG poly(A) tract will bind to Pab1p, whose binding size is 12 consecutive A residues in yeast, resulting in repression of translation. The hypothesis explains why a long pre-AUG poly(A) leads to more efficient translation initiation than a short one when PABP is absent, and why pre-AUG poly(A) is short in the early genes but long in the late genes of vaccinia virus.
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Translation initiation is typically the limiting step in translation, and its efficiency depends heavily on how rapidly the 5′-UTR can load ribosome onto the mRNA.
“Translation initiation is typically the limiting step in translation, and its efficiency depends heavily on how rapidly the 5′-UTR can load ribosome onto the mRNA [9].”
From Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines (2021) · cites this paper as [9]
The Abstract (page not provided) calls the 5′-UTR a ribosome-loading dock during initiation and a key site of translation regulation. The Results section on protein synthesis rate and ribosomal density (page not provided) uses ribosomal density as a measure of translation efficiency. Neither passage establishes that initiation is typically the limiting step or that efficiency depends specifically on the speed of ribosome loading. (LLM, conf=0.84)
Experimental — accuracy not yet measuredEfficient translation initiation in mammalian species depends mainly on the secondary structure that may embed the Kozak consensus to obscure essential translation initiation signals.
“Efficient translation initiation in mammalian species depends mainly on two factors [40,41]: (1) the Kozak consensus [42,43,44], and (2) the secondary structure that may embed the Kozak consensus to obscure these essential translation initiation signals [9,41,45].”
From Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines (2021) · cites this paper as [9]
The Discussion section on pre-AUG poly(A) and Pab1p mentions secondary-structure stability in yeast and Drosophila IRESs, but not a Kozak consensus being obscured by secondary structure. The paper’s reported analysis concerns yeast poly(A) tracts; searches for Kozak and mammalian translation initiation found no passage addressing the attributed claim. Page numbers were not available in our copy. (LLM, conf=0.72)
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Cited by
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Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines
Xia, X. (2021) · Vaccines · doi:10.3390/vaccines9070734 · Cited by 201 · see citing works
Self-citation
- Authors
- Xia, X., MacKay, V., Yao, X., Wu, J., Miura, F., Ito, T., & Morris, D. R.
- Affiliations
- University of Ottawa (CA)
- University of Washington (US)
- South China University of Technology (CN)
- The University of Tokyo (JP)
- Corresponding author
- Xia, Xuhua
- Venue
- Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-10-01
- Volume
- 189
- Issue
- 2
- Pages
- 469-478
- ISSN
- 0016-6731 (ISSN-L)
- 1943-2631
- PMC
- PMC3189813
- OpenAlex
- W2025576332
- Cited by
- 50
- References
- 2
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 6 · 2023: 2 · 2022: 1 · 2021: 2 · 2019: 4 · 2018: 10 · 2017: 3 · 2016: 4 · 2015: 2 · 2014: 3 · 2013: 3 · 2012: 4
- FWCI
- 1.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Tokyo
- Japan Society for the Promotion of Science (20310114)
- 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
- translation initiation, poly(A) tract, 5' untranslated region, Saccharomyces cerevisiae, poly(A)-binding protein, protein synthesis rate, protein abundance, translational regulation, translation initiation factors
- MeSH terms
- Base Sequence, Binding Sites, Codon, Peptide Initiation Factors, Poly A, Protein Binding, Ribosomes, Saccharomyces cerevisiae, Protein Biosynthesis, 5' Untranslated Regions, Saccharomyces cerevisiae Proteins, Poly(A)-Binding Proteins
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