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Differential Evolution of CDS and UTR Non-canonical RNA G-quadruplex Structures in Eukaryotic Transcriptomes
Eugene Yui-Ching Chow1, Jieyu Zhao2, Chun Kit Kwok2,3
1School of Life Sciences, and State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region 999077, China.
Genomics, Proteomics & Bioinformatics
|September 19, 2025
Summary
RNA G-quadruplexes (rG4s), crucial RNA structures, have evolved significantly over a billion years. Non-canonical rG4s dominate eukaryotic transcriptomes, with untranslated region rG4s increasingly favored over coding regions.
Area of Science:
- Molecular Biology
- Genomics
- Evolutionary Biology
Background:
- RNA G-quadruplexes (rG4s) are four-stranded RNA structures with regulatory roles.
- While canonical rG4s are well-studied, non-canonical forms are increasingly recognized for their importance.
- Understanding rG4 evolution provides insights into gene regulation.
Purpose of the Study:
- To experimentally determine and bioinformatically analyze rG4 structures across eukaryotic species.
- To investigate the evolutionary trajectory and compositional dynamics of rG4s over one billion years.
- To differentiate evolutionary patterns between coding sequence (CDS) and untranslated region (UTR) rG4s.
Main Methods:
- Experimental determination of rG4 structures.
- Large-scale bioinformatic analysis of rG4omes across eukaryotic species.
- Comparative evolutionary analysis of CDS and UTR rG4s.
Main Results:
- rG4s are an integral part of eukaryotic transcriptomes, with non-canonical forms predominating.
- The rG4ome has expanded over evolutionary time, shifting towards UTR rG4s over CDS rG4s.
- Distinct evolutionary patterns were observed for CDS and UTR rG4s, including rapid UTR rG4 emergence in mammals.
Conclusions:
- Non-canonical rG4s are evolutionarily conserved and increasingly prevalent in eukaryotes.
- The shift towards UTR rG4s and specific evolutionary dynamics in mammals are key findings.
- This study provides a comprehensive view of rG4 evolution and highlights the importance of non-canonical structures.
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