RNA G-quadruplex formation in biologically important transcribed regions: can two-tetrad intramolecular RNA quadruplexes be formed?
G-quadruplexes (G4s) formed within RNA are emerging as promising targets for therapeutic intervention in cancer, neurodegenerative disorders and infectious diseases. Sequences containing a succession of short GG blocks, or uneven G-tract lengths unable to form three-tetrad G4s (GG motifs), are overwhelmingly more frequent than canonical motifs involving multiple GGG blocks. We recently showed that DNA is not able to form stable two-tetrad intramolecular parallel G4s. Whether RNA GG motifs can form intramolecular G4s under physiological conditions and play regulatory roles remains a burning question. In this study, we performed a systematic analysis and experimental evaluation of a number of biologically important RNA regions involving RNA GG motifs. We show that most of these motifs do not form stable intramolecular G4s but need to dimerize to form stable G4 structures. The strong tendency of RNA GG motif G4s to associate may participate in RNA-based aggregation under conditions of cellular stress.
Authors
- Iva Kejnovská (ORCID: https://orcid.org/0000-0001-7380-9925)
- Jean‐Louis Mergny (ORCID: https://orcid.org/0000-0003-3043-8401)
- Lukáš Trantı́rek (ORCID: https://orcid.org/0000-0001-5948-4837)
- Denis Šubert (ORCID: https://orcid.org/0000-0002-6455-0445)
- Michaela Vorlı́čková
- Pritha Basu
- Martin Gajarský (ORCID: https://orcid.org/0000-0003-2036-6512)
- Daniel Renčiuk (ORCID: https://orcid.org/0000-0001-9293-7105)
- Tereza Mikešová
Institutions
- Centre National de la Recherche Scientifique (FR)
- Central European Institute of Technology (CZ)
- École Polytechnique (FR)
- Inserm (FR)
- University of Cologne (DE)
- Masaryk University (CZ)
- Czech Academy of Sciences, Institute of Biophysics (CZ)
- Central European Institute of Technology – Masaryk University (CZ)
Publication Details
- Journal
- Nucleic Acids Research
- Published
- 2024-11-04
- DOI
- https://doi.org/10.1093/nar/gkae927
- Citations
- 22
- Primary Topic
- DNA and Nucleic Acid Chemistry
- Type
- article
- Field-Weighted Citation Impact
- 5.14
Funders
- Deutsche Forschungsgemeinschaft
- Institut National de la Santé et de la Recherche Médicale
- Ministerstvo Školství, Mládeže a Tělovýchovy
- Grantová Agentura České Republiky
- Centre National de la Recherche Scientifique
- European Regional Development Fund