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Updated: Dec 17, 2025

Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells
Published on: December 9, 2022
Making ends meet: New functions of mRNA secondary structure
Dmitri N Ermolenko1, David H Mathews1
1Department of Biochemistry & Biophysics and Center for RNA Biology, School of Medicine and Dentistry, University of Rochester, Rochester, New York, USA.
Abstract:
The 5' cap and 3' poly(A) tail of mRNA are known to synergistically regulate mRNA translation and stability. Recent computational and experimental studies revealed that both protein-coding and non-coding RNAs will fold with extensive intramolecular secondary structure, which will result in close distances between the sequence ends. This proximity of the ends is a sequence-independent, universal property of most RNAs. Only low-complexity sequences without guanosines are without secondary structure and exhibit end-to-end distances expected for RNA random coils. The innate proximity of RNA ends might have important biological implications that remain unexplored. In particular, the inherent compactness of mRNA might regulate translation initiation by facilitating the formation of protein complexes that bridge mRNA 5' and 3' ends. Additionally, the proximity of mRNA ends might mediate coupling of 3' deadenylation to 5' end mRNA decay. This article is categorized under: RNA Structure and Dynamics > RNA Structure, Dynamics, and Chemistry RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems Translation > Translation Regulation.
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