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Updated: Jan 21, 2026

RNA Secondary Structure Prediction Using High-throughput SHAPE

RNA Secondary Structure Prediction Using High-throughput SHAPE

Published on: May 31, 2013

Sequence-dependent RNA helix conformational preferences predictably impact tertiary structure formation.

Joseph D Yesselman¹, Sarah K Denny², Namita Bisaria¹

¹Department of Biochemistry, Stanford University, Stanford, CA 94305.

Proceedings of the National Academy of Sciences of the United States of America

|August 4, 2019

Summary

This summary is machine-generated.

RNA helix sequence changes significantly impact RNA tertiary structure stability, contrary to common assumptions. A computational model accurately predicts these effects, validated by high-throughput experiments.

Keywords:

RNA energetics blind prediction high-throughput data indirect readout

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A Protocol for Computer-Based Protein Structure and Function Prediction

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Published on: November 3, 2011

Area of Science:

Molecular Biology
Biophysics
Computational Biology

Background:

Structured RNAs are crucial for gene expression and protein translation.
Watson-Crick (WC) base pairs form approximately 50% of nucleotides in structured RNAs.
Sequence changes preserving WC pairs are often assumed to maintain RNA structure and function.

Purpose of the Study:

To investigate the impact of RNA helix sequence on tertiary structure stability.
To determine if these effects are predictable using computational models.
To provide a framework for understanding RNA structure formation and stability.

Main Methods:

Utilized the RNAMake-∆∆G computational model.
Employed the RNA on a massively parallel array (RNA-MaP) experimental platform.
Tested over 1500 variants of the tectoRNA heterodimer model system.

Main Results:

Indirect effects of helix sequence on RNA tertiary stability are significant and predictable.
RNAMake-∆∆G model achieved high accuracy in blind predictions (rmsd 0.34 kcal/mol for sequence, 0.77 kcal/mol for length changes).
Experiments revealed how helix sequence modulates conformational fluctuations impacting overall RNA stability.

Conclusions:

RNA helix sequence subtly influences tertiary structure stability through base-pair step dynamics.
This study uncovers a previously unrecognized phenomenon in RNA structure formation.
Developed a combined computational and experimental framework for analyzing RNA conformational preferences and stability.