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Updated: Jun 26, 2025
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Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells
Published on: December 9, 2022
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Structure of the SARS-CoV-2 Frameshift Stimulatory Element with an Upstream Multibranch Loop
Jake M Peterson1, Scott T Becker1, Collin A O'Leary1
1Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, Iowa 50011, United States.
Biochemistry
|May 10, 2024
Summary
The SARS-CoV-2 frameshift stimulatory element (FSE) has dynamic structures crucial for viral replication. New cryo-EM data reveals a linear pseudoknot and a flexible upstream loop, offering insights into -1 PRF.
Area of Science:
- Molecular Biology
- Virology
- Structural Biology
Background:
- The SARS-CoV-2 frameshift stimulatory element (FSE) is essential for programmed -1 ribosomal frameshifting (-1 PRF), enhancing viral efficacy.
- The FSE adopts various conformations, with an attenuator hairpin and an H-type pseudoknot being critical for -1 PRF.
Purpose of the Study:
- To elucidate the structural context of the SARS-CoV-2 FSE using computational and cryo-electron microscopy (cryo-EM) methods.
- To model a previously uncharacterized conformation involving an extended upstream multibranch loop.
Main Methods:
- Medium resolution cryo-electron microscopy (cryo-EM) at 6.1 Å resolution.
- Computational modeling approaches.
Main Results:
- A 6.1 Å cryo-EM structure revealed a linear pseudoknot conformation of the FSE.
- A dynamic upstream multibranch loop, incorporating the attenuator hairpin and slippery site, was characterized.
Conclusions:
- The study presents a novel structural model for the SARS-CoV-2 FSE, including its dynamic upstream elements.
- These findings provide crucial structural context for understanding the mechanism of -1 PRF and optimizing antiviral strategies.
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