The R-loop grammar predicts R-loop formation under different topological constraints
R-loops are transient three-stranded nucleic acids that form during transcription when the nascent RNA hybridizes with the template DNA, freeing the non-template strand of the DNA. There is growing evidence that R-loops play important roles in physiological processes such as the regulation of gene expression, and that they contribute to chromosomal instability and disease. It is known that R-loop formation is influenced by both the sequence and the topology of the DNA substrate, but many questions remain about how R-loops form and the three-dimensional structures that they adopt. Here we represent an R-loop as a word in a formal grammar, the R-loop grammar. We use the R-loop grammar to predict R-loop formation. We train the R-loop grammar on experimental data obtained by single-molecule R-loop footprinting and sequencing (SMRF-seq). Despite not explicitly encoding topological information, the R-loop grammar accurately predicts R-loop formation on plasmids with varying starting topologies and outperforms previous methods in R-loop prediction.
Authors
- Manda Riehl (ORCID: https://orcid.org/0000-0003-4129-4044)
- Stella R. Hartono (ORCID: https://orcid.org/0000-0001-6234-3445)
- Jacob Lusk
- Margherita Maria Ferrari (ORCID: https://orcid.org/0000-0002-9780-363X)
- Frédéric Chédin (ORCID: https://orcid.org/0000-0002-1306-5335)
- Svetlana Poznanović (ORCID: https://orcid.org/0000-0002-8229-8220)
- Nataša Jonoska
- Mariel Vázquez (ORCID: https://orcid.org/0000-0001-8328-6806)
- Georgina Gonzalez-Isunza
Institutions
- Rose–Hulman Institute of Technology (US)
- University of South Florida (US)
- University of Manitoba (CA)
- Clemson University (US)
- University of California, Davis (US)
Publication Details
- Journal
- PLoS Computational Biology
- Published
- 2025-08-29
- DOI
- https://doi.org/10.1371/journal.pcbi.1013376
- Citations
- 1
- Primary Topic
- RNA and protein synthesis mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- National Science Foundation
- W. M. Keck Foundation
- Simons Foundation
- Association for Women in Mathematics
- University of Manitoba
- National Institutes of Health
- Directorate for Computer and Information Science and Engineering
- Directorate for Mathematical and Physical Sciences
- Natural Sciences and Engineering Research Council of Canada
- National Institute of General Medical Sciences