The mRNA landscape at yeast translation initiation sites
Open accessAbstract
Summary: Although translation initiation has been well studied, many questions remain in elucidating its mechanisms. An ongoing challenge is to understand how ribosomes choose a translation initiation site (TIS). To gain new insights, we analyzed large sets of TISs with the aim of identifying common characteristics that are potentially of functional importance. Nucleotide sequence context has previously been demonstrated to play an important role in the ribosome's selection of a TIS, and mRNA secondary structure is also emerging as a contributing factor. Here, we analyze mRNA secondary structure using the folding predictions of the RNAfold algorithm. We present a method for analyzing these results using a rank-ordering approach to assess the overall degree of predicted secondary structure in a given region of mRNA. In addition, we used a modified version of the algorithm that makes use of only a subset of the standard version's output to incorporate base-pairing polarity constraints suggested by the ribosome scanning process. These methods were employed to study the TISs of 1735 genes in Saccharomyces cerevisiae. Trends in base composition and base-pairing probabilities suggest that efficient translation initiation and high protein expression are aided by reduced secondary structure upstream and downstream of the TIS. However, the downstream reduction is not observed for sets of TISs with nucleotide sequence contexts unfavorable for translation initiation, consistent with previous suggestions that secondary structure downstream of the ribosome can facilitate TIS recognition. Contact: mweir@wesleyan.edu Supplementary Information: Supplementary data are available at Bioinformatics online.
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For highly translated proteins, the study found a conservation pattern similar to prior work, with lysine (AAA) and serine (TCT) most frequent just before and after the start codon, respectively.
“we found a similar conservation pattern for the highly translated proteins (Gingold and Pilpel, 2011; Ingolia et al., 2009; Robbins-Pianka et al., 2010), where lysine (encoded by AAA) and serine (encoded by TCT) were the most frequently observed amino acids just before and after the start codon, respectively.”
From Absolute Quantification of Protein and mRNA Abundances Demonstrate Variability in Gene-Specific Translation Efficiency in Yeast (2017) · cites this paper as Robbins-Pianka et al., 2010
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- Authors
- Robbins-Pianka, A., Rice, M. D., & Weir, M. P.
- Affiliations
- 1 Department of Biology and 2Department of Mathematics and Computer Science, Wesleyan University, Middletown, CT 06459, USA
- Wesleyan University (US)
- Corresponding author
- Weir, M. P.
- ORCID
- Weir, M. P.
- Venue
- Bioinformatics
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-09-06
- Volume
- 26
- Issue
- 21
- Pages
- 2651-2655
- ISSN
- 1367-4803 (ISSN-L)
- 1367-4811
- OpenAlex
- W2142142506
- Cited by
- 39
- References
- 28
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 5 · 2016: 2 · 2015: 2 · 2014: 4 · 2013: 6 · 2012: 4
- FWCI
- 1.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Bioinformatics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- 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
- translation initiation sites, mRNA secondary structure, ribosome scanning, RNA folding prediction, RNAfold, Saccharomyces cerevisiae, protein expression
- MeSH terms
- Algorithms, Genes, Fungal, Nucleic Acid Conformation, RNA, Messenger, Saccharomyces cerevisiae, Protein Biosynthesis, Computational Biology
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