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Updated: Jun 5, 2025

Artificial RNA Polymerase II Elongation Complexes for Dissecting Co-transcriptional RNA Processing Events
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Tree polynomials identify a link between co-transcriptional R-loops and nascent RNA folding.

Pengyu Liu1, Jacob Lusk1, Nataša Jonoska2

  • 1Department of Microbiology and Molecular Genetics, University of California, Davis, Davis, California, United States of America.

Plos Computational Biology
|December 13, 2024
PubMed
Summary
This summary is machine-generated.

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Researchers developed a computational pipeline using tree-polynomials to predict R-loop formation. This method links RNA secondary structures to R-loop occurrence, identifying specific structural features associated with these nucleic acid structures.

Area of Science:

  • Molecular Biology
  • Bioinformatics
  • Genetics

Background:

  • R-loops are non-canonical nucleic acid structures crucial in biological processes.
  • Formation of R-loops is influenced by DNA sequence and topology, but the exact mechanisms are not fully understood.
  • Investigating the role of nascent RNA folding in R-loop formation is essential for understanding their function and regulation.

Purpose of the Study:

  • To investigate the link between nascent RNA folding and R-loop formation.
  • To develop a computational method for predicting R-loop formation based on genomic sequences.
  • To identify specific RNA secondary structure features associated with R-loop formation.

Main Methods:

  • Introduction of tree-polynomials, a novel representation for RNA secondary structures without pseudoknots.

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  • Development of a computational pipeline integrating co-transcriptional RNA folding software and tree-polynomial analysis.
  • Application of the pipeline to plasmid sequences containing R-loop forming genes.

    • Main Results:

    • A strong correlation was established between the coefficient sums of tree-polynomials and the experimental probability of R-loop formation.
    • The computational pipeline demonstrated high accuracy in predicting R-loop formation.
    • Specific RNA secondary structure features, including branches with short stems and intervening bulges/loops, were identified as associated with R-loops.

    Conclusions:

    • The developed tree-polynomial approach provides an accurate and interpretable method for predicting R-loop formation.
    • Nascent RNA secondary structure plays a significant role in the formation of R-loops.
    • The findings offer insights into the structural determinants of R-loop formation, aiding further research in nucleic acid structure and function.