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Study of the impact and global role of RNA G-quadruplexes in transcriptome

 
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The life of an mRNA is dotted with several maturation and regulatory events. For a long time, it was generally accepted that the main way of regulating gene expression was at the transcriptional level. However, it has recently been reported that 90% of our genome is transcribed into RNA. Following this new discovery, it is logical to think that it is rather the post-transcriptionnal regulation that is the centerpiece of gene expression. The G-quadruplex structure is adopted by nucleic acid molecules rich in guanines. This structure is formed of a stack of "G-quartets" which are composed of 4 coplanar guanines and require the presence of monovalent metal cations, usually K +. The recognition of G-quadruplexes as regulatory elements found in the genome begins to be established. However, the majority of research in this regard focuses on G-quadruplex DNA and only very little on those composed of RNA. Thanks to its 3 different phases (in silico, in vitro and in cellulo), our approach allowed us to evaluate the global role of G-quadruplexes of RNA in the cell, more specifically at the level of untranslated regions of mRNAs.

In addition to their effect on translation, some RNA G-quadruplexes are able to modulate the regulation of polyadenylation, alternative splicing, and the maturation of microRNAs. Some G-quadruplexes are also known to influence mRNA localization.

Our research results allow the identification of new G-quadruplexes, notably through the use of artificial intelligence. By automated learning, we are now able to identify new G-quadruplexes in any genome. Finally, it is also possible for us to promote or prevent the formation of a G-quadruplex in the cell by using specific oligonucleotides. As a result, RNA G-quadruplexes become potential new therapeutic targets.