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Stimulation of ribosomal frameshifting by RNA G-quadruplex structures
Chien-Hung Yu1, Marie-Paule Teulade-Fichou, René C L Olsthoorn
1Department of Molecular Genetics, Leiden Institute of Chemistry, Leiden University, PO Box 9502, Leiden, The Netherlands and Institut Curie, UMR 176-CNRS, Bât 110, Université Paris-Sud, 91405 Orsay, France.
Nucleic Acids Research
|November 2, 2013
Summary
RNA G-quadruplexes (G4) can regulate gene expression by influencing ribosomal frameshifting. This study shows G4 RNA structures stimulate -1 ribosomal frameshifting and other translational events, suggesting a new gene regulation mechanism.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Guanine-rich sequences form G-quadruplexes (G4), extensively studied in DNA.
- The biological roles of RNA G-quadruplexes are an emerging area of research.
Purpose of the Study:
- To investigate the functional role of RNA G-quadruplexes in gene expression.
- To determine if RNA G4 structures can influence ribosomal frameshifting.
Main Methods:
- In vitro and cell-based assays were used to study RNA G-quadruplexes.
- Systematic manipulation of loop lengths in G-tracts was performed.
- The effect of a G4-stabilizing ligand (PhenDC3) was assessed.
Main Results:
- RNA G-quadruplexes within coding regions stimulate -1 ribosomal frameshifting (-1 FS).
- Frameshifting efficiency positively correlates with G4 stability.
- G4 RNA also stimulates +1 FS and stop codon readthrough.
Conclusions:
- RNA G-quadruplexes represent a novel mechanism for translational gene regulation.
- G4 RNA stability is a key factor in modulating frameshifting efficiency.
- These findings open new avenues for understanding gene expression control.
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