Publication Date
12-19-2025
Document Type
Article
Organizational Units
College of Natural Science and Mathematics, Chemistry and Biochemistry
Keywords
RNA nanostructures, Self assembly, Atomic force microscopy, Light scattering
Abstract
Recent developments in RNA nanotechnology have led to an increase in the design of specific, higher-order RNA structures, which will ultimately be used in drug delivery and immunomodulation applications. As researchers create RNA nanostructures with the intention of making them a standard tool in molecular biologists' toolkits, further investigation is required into the robustness of RNA designs. Primarily, in what different molecular contexts are the designed and intended nanostructures stable? In this work, we show that RNA nanostructure self-assembly is highly sensitive to environmental conditions by using second-order right-angle light scattering. While a test RNA hexagonal grid nanostructure forms correctly through 120° kissing loops under ideal conditions, small variations in salt conditions and annealing times cause the nanostructure to form less structured variants. Tertiary contacts for self-assembly require magnesium and break over a broad range of low temperatures, melting at 43 °C. In contrast, this was found to be considerably lower than the secondary structure melting, which occurred at 75 °C. This work highlights the importance of quantitatively and thermodynamically characterizing self-assembling nanostructures as they are increasingly deployed for engineering and therapeutic applications.
Copyright Date
1-6-2026
Copyright Statement / License for Reuse

This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 International License.
Rights Holder
Jordan Aposhian, Surya Pratap S. Deopa, Scott Horowitz, and Joseph D. Yesselman
Provenance
Received from Elsevier
File Format
application/pdf
Language
English (eng)
Extent
13 pgs
File Size
4.00 MB
Publication Statement
Copyright is held by the Authors. User is responsible for all copyright compliance. This article was originally published as
Aposhian, J., Deopa, S. P. S., Horowitz, S., & Yesselman, J. D. (2026). Self-Assembling RNA Nanostructures are Highly Sensitive to Environmental Conditions. Journal of Molecular Biology, 438(5). https://doi.org/10.1016/j.jmb.2025.169601
Supplementary File Description
"Graphical Abstract", JPG File, 1 Image, 133 KB
Publication Title
Journal of Molecular Biology
Volume
438
Issue
5
First Page
169601
ISSN
0022-2836
PubMed ID
41422840
Recommended Citation
Aposhian, Jordan; Deopa, Surya Pratap S.; Horowitz, Scott; and Yesselman, Joseph D., "Self-Assembling RNA Nanostructures are Highly Sensitive to Environmental Conditions" (2025). Chemistry and Biochemistry: Faculty Scholarship. 131.
https://digitalcommons.du.edu/chemistryandbiochemistryfaculty/131
https://doi.org/10.1016/j.jmb.2025.169601