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The roles of deoxyribonucleic acid (DNA) G-quadruplex structures in gene expression and telomere maintenance have been well characterized. Recent results suggest that such structures could also play pivotal roles in ribonucleic acid (RNA) biology, such as splicing or translation regulation. However, it has been difficult to show that RNA G-quadruplexes (G4s) exist in specific long RNA sequences, such as precursor messenger RNA, in a functional or cellular context. Most current methods for identifying G4s involve the use of short, purified RNA sequences in vitro, in the absence of competition with secondary structures or protein binding. Therefore, novel methods need to be developed to allow the characterization of G4s in long functional RNAs and in a cellular context. This need has in part been met by our recent development of a method based on a comparison of RNA and 7-deaza-RNA that provides a test for identifying RNA G4s in such conditions.

Do we know whether potential G-quadruplexes actually form in long functional RNA molecules?