Consequences of mRNA Secondary Structure on Stability against both Hydrolysis and Aggregation: The Role of Electrostatic, π–π Stacking, and Thermal Effects
Curtis W. Jarand, Zhiyou Deng, Mark L. Brader, Wayne F. Reed
TL;DR
This paper explores how mRNA's secondary structure affects its stability against breakdown and clumping, revealing new insights into the role of electrostatic and stacking forces.
Contribution
The study links mRNA aggregation and autohydrolysis through secondary structure effects, introducing a new model involving electrostatic and π–π stacking interactions.
Findings
mRNA secondary structure stabilizes against autohydrolysis and aggregation.
Guanidine-HCl and temperature destabilize mRNA structure, increasing aggregation and hydrolysis.
A new model explains aggregation via electrostatic and π–π stacking effects.
Abstract
The seemingly unrelated massive aggregation of free mRNA under certain solution conditions and the well-known autohydrolysis of mRNA are actually both closely linked through its secondary and possibly tertiary structure (s/t). This hypothesis posits that s/t partially stabilizes mRNA against both autohydrolysis and massive aggregation. Destabilization of s/t via denaturant guanidine-HCl (Gd), or temperature, has profound effects on both aggregation rates and final degree of autohydrolysis. These denaturant effects occurred for a variety of mRNA, ranging from 700 to 3000 nucleotides but showed very different quantitative behavior among themselves, suggesting some of the methods presented here might help characterize mRNA stability and robustness. Light scattering monitoring during dialysis of mRNA against Gd revealed an “aggregation window”, over 0.5–3 M Gd, whereas dialyzing against a…
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Taxonomy
TopicsRNA Research and Splicing · Force Microscopy Techniques and Applications · Electrostatics and Colloid Interactions