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Aptamer-Based Target Detection Facilitated by a 3-Stage G-Quadruplex Isothermal Exponential Amplification Reaction
Published on: October 6, 2022
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Small molecule-based detection of non-canonical RNA G-quadruplex structures that modulate protein translation
Yousuke Katsuda1, Shin-Ichi Sato2, Maimi Inoue1
1Division of Materials Science and Chemistry, Faculty of Advanced Science and Technology, Kumamoto University, 2-39-1 Kurokami, Chuo-ku, Kumamoto 860-8555, Japan.
Nucleic Acids Research
|July 8, 2022
Summary
Researchers developed a new method to detect RNA G-quadruplexes, revealing their role in controlling protein translation. This study identified specific genes, Nectin-4 and CapG, regulated by these structures in human cells.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Guanine-rich RNA sequences can form stable four-stranded RNA G-quadruplex structures.
- The physiological significance of RNA G-quadruplexes in cellular processes, particularly protein translation, remains largely undetermined.
Purpose of the Study:
- To develop and apply a novel approach for detecting RNA G-quadruplexes that influence protein translation in mammalian cells.
- To identify specific genes and their RNA structures involved in G-quadruplex-mediated translational control.
Main Methods:
- Utilized a combination of antibody arrays and RGB-1, a small molecule that selectively stabilizes RNA G-quadruplexes.
- Analyzed protein and mRNA products from 84 cancer-related human genes.
Main Results:
- Identified Nectin-4 and CapG as genes whose translation is controlled by RNA G-quadruplexes.
- Discovered non-canonical RNA G-quadruplex structures in the 5' untranslated region (5'UTR) of Nectin-4 and CapG mRNAs.
- Observed structural polymorphism in the CapG RNA G-quadruplex, potentially regulating translation repression under varying KCl concentrations (25-100 mM).
Conclusions:
- The developed approach enables the detection of functionally relevant RNA G-quadruplexes modulating protein translation.
- RNA G-quadruplexes play a significant role in regulating gene expression at the translational level.
- This work provides a foundation for future discoveries of RNA G-quadruplex functions in biological systems.
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