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Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
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Group II Intron RNPs and Reverse Transcriptases: From Retroelements to Research Tools.
Marlene Belfort1, Alan M Lambowitz2
1Department of Biological Sciences and RNA Institute, University at Albany, State University of New York, Albany, New York 12222.
Cold Spring Harbor Perspectives in Biology
|April 3, 2019
Summary
Group II introns are key retrotransposons for genome editing. This study reveals their cryo-EM structure, introduces RIG-seq for integration profiling, and details thermostable reverse transcriptases for RNA-seq applications.
Area of Science:
- Molecular Biology
- Structural Biology
- Genomics
Background:
- Group II introns are mobile genetic elements with roles in RNA splicing and genome mobility.
- They are also utilized as tools for genome engineering and RNA analysis.
Purpose of the Study:
- To determine the cryo-electron microscopy (cryo-EM) structure of a group II intron ribozyme complexed with its reverse transcriptase (RT).
- To introduce RIG-seq for high-throughput integration profiling of retrotransposons.
- To characterize thermostable group II intron RTs for RNA sequencing (RNA-seq) applications.
Main Methods:
- Cryo-electron microscopy (cryo-EM) for structural determination.
- RIG-seq (retrotransposon indicator gene) for integration profiling.
- Biochemical characterization and X-ray crystallography of reverse transcriptases.
Main Results:
- First cryo-EM structure of a group II intron-protein complex at 3.8-4.5 Å resolution.
- Development of RIG-seq for efficient retrotransposon integration site analysis.
- Characterization of highly accurate and processive thermostable group II intron RTs, with a 3.0-Å crystal structure.
Conclusions:
- Structural and functional insights into group II introns and their encoded proteins.
- Advancements in tools for studying retrotransposon dynamics and genome engineering.
- Thermostable RTs offer improved capabilities for RNA-seq and related applications.
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