The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
40S ribosomal subunits scan mRNA for the start codon by one-dimensional diffusion
Open accessPublished version of a preprint
Abstract
During eukaryotic translation initiation, the small (40S) ribosomal subunit is recruited to the 5ʹ cap and subsequently scans the 5ʹ untranslated region (5ʹ UTR) of mRNA in search of the start codon. The molecular mechanism of mRNA scanning remains unclear, particularly the requirement for and identity of a translocase. Here, using GFP reporters in Saccharomyces cerevisiae, we show that order-of-magnitude variations in the length of unstructured 5ʹ UTRs have only modest effects on protein synthesis, while structured 5’ UTRs strongly inhibit translation. Thus, when not hindered by secondary structure, mRNA scanning is not rate limiting. Loss-of-function mutations in eIF4A, Ded1 and Slh1 reveal that these translational helicases are dispensable for mRNA scanning. Our data suggest that one-dimensional diffusion predominately enables 40S movement along the 5ʹ UTR during mRNA scanning.
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Citations
Cites
Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566 · cited 1×
“…believed to move along the 5 ′ UTR (Kozak and Shatkin 1978a,b; Kozak 1979; Archer et al. 2016) in search of the start codon. mRNAs vary in their translational efficiencies by at least two orders of magnitude (Arava et al. 2003; Ingolia et al. 2009; Schwanhausser et al. 2011; Weinberg et al. 2016).”
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Metadata
- Authors
- Wakabayashi, H., Zhu, M., Grayhack, E. J., Mathews, D. H., & Ermolenko, D. N.
- Affiliations
- University of Rochester Medicine (US)
- Corresponding author
- Ermolenko, Dmitri N
- Venue
- RNA
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2025-07-31
- Volume
- 31
- Issue
- 10
- Pages
- rna.080493.125
- ISSN
- 1355-8382 (ISSN-L)
- 1469-9001
- PMC
- PMC12415969
- OpenAlex
- W4412797962
- Cited by
- 0
- References
- 1
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- RNA (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (1s10od021489-01a1)
- National Institute of General Medical Sciences (R35GM141812, R35GM145283)
- 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
- 40S ribosomal subunit, mRNA scanning, translation initiation, 5' untranslated region, one-dimensional diffusion, eIF4A, Ded1, mRNA secondary structure, 5' cap, Saccharomyces cerevisiae
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