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Cited by 255DNA and Nucleic Acid ChemistryRNA and protein synthesis mechanismsRNA Research and Splicing

5′-UTR G-quadruplex structures acting as translational repressors

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Beaudoin, J.-D., Perreault, J.-P.·2010·Nucleic Acids Research
DOI 10.1093/nar/gkq557PMC PMC2978341
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Abstract

Given that greater than 90% of the human genome is expressed, it is logical to assume that post-transcriptional regulatory mechanisms must be the primary means of controlling the flow of information from mRNA to protein. This report describes a robust approach that includes in silico, in vitro and in cellulo experiments permitting an in-depth evaluation of the impact of G-quadruplexes as translational repressors. Sequences including potential G-quadruplexes were selected within nine distinct genes encoding proteins involved in various biological processes. Their abilities to fold into G-quadruplex structures in vitro were evaluated using circular dichroism, thermal denaturation and the novel use of in-line probing. Six sequences were observed to fold into G-quadruplex structures in vitro, all of which exhibited translational inhibition in cellulo when linked to a reporter gene. Sequence analysis, direct mutagenesis and subsequent experiments were performed in order to define the rules governing the folding of G-quadruplexes. In addition, the impact of single-nucleotide polymorphism was shown to be important in the formation of G-quadruplexes located within the 5'-untranslated region of an mRNA. In light of these results, clearly the 5'-UTR G-quadruplexes represent a class of translational repressors that is broadly distributed in the cell.

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  • Some mRNAs with a long 5′UTR and high GC content are actively translated via a cap-dependent mechanism; the 5′UTR of LINE1 mRNA (900-nt, 60% GC content) is an example.

    “By contrast, there are mRNAs with a long 5′UTR that has a high GC content, and yet these mRNAs are actively translated via a cap-dependent mechanism; the 5′UTR of LINE1 mRNA is an example (900-nt 5′UTR with a 60% GC content) [8].”

    From Effects of Combinations of Untranslated-Region Sequences on Translation of mRNA (2023) · cites this paper as [8]

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Authors
Beaudoin, J.-D., & Perreault, J.-P.
Affiliations
Université de Sherbrooke (CA)
Corresponding author
Perreault, J.-P.
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2010-06-22
Volume
38
Issue
20
Pages
7022-7036
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkq557
PMC
PMC2978341
OpenAlex
W2074613554
Cited by
255
References
1
Citations by year
2026: 9 · 2025: 16 · 2024: 23 · 2023: 14 · 2022: 19 · 2021: 18 · 2020: 17 · 2019: 15 · 2018: 13 · 2017: 14 · 2016: 23 · 2015: 13 · 2014: 18 · 2013: 13 · 2012: 15
FWCI
5.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
Canadian Institutes of Health Research (44002, 80169_1, 44022_1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
  • 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
Keywords
G-quadruplex, 5' untranslated region, protein synthesis inhibition, post-transcriptional regulation, mRNA secondary structure, G-quadruplex folding, single nucleotide polymorphisms, circular dichroism, thermal denaturation, reporter genes
MeSH terms
Humans, Protein Biosynthesis, 5' Untranslated Regions, Regulatory Sequences, Ribonucleic Acid, G-Quadruplexes

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