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Cited by 246RNA and protein synthesis mechanismsRNA Research and SplicingFungal and yeast genetics research

Deciphering the rules by which 5′-UTR sequences affect protein expression in yeast

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Dvir, Shlomi, Velten, Lars, Sharon, Eilon, Zeevi, Danny, Carey, Lucas B., Weinberger, Adina, Segal, Eran·2013·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1222534110PMC PMC3725075
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Abstract

Significance: This study quantifies how protein levels are determined by the underlying 5′-UTR sequence of an mRNA. We accurately measured protein abundance in 2,041 5′-UTR sequence variants, differing only in positions −10 to −1. We show that a few nucleotide substitutions can significantly alter protein expression. We also developed a predictive model that explains two-thirds of the expression variation. We provide convincing evidence that key regulatory elements, including AUG sequence context, mRNA secondary structure, and out-of-frame upstream AUGs conjointly modulate protein levels. Our study can aid in synthetic biology applications, by suggesting sequence manipulations for fine-tuning protein expression in a predictable manner.

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Crossref · 10.1073/pnas.1222534110

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  • Stable secondary structure in the 5′-UTR before or flanking the start codon decreases protein production.

    “As demonstrated in previous studies on translation initiation in yeast [55] and in mouse cell lines [56], stable secondary structure in the 5′-UTR before or flanking the start codon decreases protein production.”

    From Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines (2021) · cites this paper as [55]

    The Results (Fig. 3; page unavailable) report that more stable structures near the start codon are associated with reduced protein levels in yeast. But the paper describes this as a correlation and says such structures may impede ribosomal scanning; it does not demonstrate that the structures themselves cause the decrease asserted in the citing sentence. (LLM, conf=0.85)

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Research works printed but not linked: 60

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Authors
Dvir, S., Velten, L., Sharon, E., Zeevi, D., Carey, L. B., Weinberger, A., & Segal, E.
Affiliations
  • Weizmann Institute of Science (IL)
  • European Molecular Biology Laboratory (DE)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2013-07-05
Volume
110
Issue
30
Pages
E2792-801
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1222534110
PMC
PMC3725075
OpenAlex
W2000137108
Cited by
246
References
3
Citations by year
2026: 15 · 2025: 15 · 2024: 15 · 2023: 16 · 2022: 20 · 2021: 17 · 2020: 28 · 2019: 23 · 2018: 18 · 2017: 25 · 2016: 23 · 2015: 19 · 2014: 11 · 2013: 1
FWCI
6.78
Type
journal article
Language
en
Update notices
correction (2019-06-17)
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ca119176-10)
  • National Human Genome Research Institute (R01HG004361)
  • National Cancer Institute (R01-CA119176)
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 › Fungal and yeast genetics research
Keywords
5' untranslated region, mRNA secondary structure, protein abundance, upstream AUGs, translational regulation, yeast, next-generation sequencing, nucleotide composition, translation initiation sites
MeSH terms
Base Sequence, Fungal Proteins, Nucleic Acid Conformation, RNA, Messenger, Saccharomyces cerevisiae, DNA Primers, Codon, Initiator, 5' Untranslated Regions

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