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The structure, folding kinetics, and dynamics of long poly(UG) RNA
Riley J Petersen1, Rahul Vivek1, Marco Tonelli1,2
1Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, United States.
Nucleic Acids Research
|July 19, 2025
Summary
Long poly(UG) repeats form stable quadruplex structures crucial for gene silencing. These RNA structures fold slowly but unfold very gradually, revealing complex dynamics important for biological functions.
Area of Science:
- Molecular Biology
- RNA Structure and Dynamics
- Gene Regulation
Background:
- Long poly(UG) dinucleotide repeats (pUGs) are prevalent in eukaryotic transcriptomes, with over a thousand human genes containing such repeats.
- The cancer-associated lncRNA NEAT1 is one example of a gene featuring long pUGs.
- In C. elegans, enzymatic addition of long pUGs to RNA 3' ends (pUG tails) serves as a mechanism for gene silencing, with longer tails being more effective.
Purpose of the Study:
- To investigate the structural properties, folding kinetics, and dynamics of long poly(UG) RNAs.
- To elucidate the mechanism of double pUG fold formation and its relationship to RNA dynamics.
Main Methods:
- In vitro analysis of RNA folding kinetics for RNAs with 24 or more repeats.
- Measurement of folding and unfolding rates using techniques to assess structural stability.
- Characterization of RNA dynamics through biphasic kinetic analysis.
Main Results:
- Long pUG RNAs (≥24 repeats) slowly form compact, double pUG folds.
- Fold formation is slow (t1/2 ≥ 13 min), while unfolding is very slow (t1/2 ≈ 5 days), indicating high stability.
- Biphasic dynamics reveal a faster partial unfolding phase (t1/2 ≈ 30 min), suggesting dynamic structural rearrangements.
Conclusions:
- A dynamic model for segmental register exchange and double pUG fold formation in long pUG RNAs is proposed.
- The study enhances understanding of the structure and dynamics of long pUG RNAs.
- Findings have implications for the biological roles and disease relevance of pUG folds.
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