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Long-range RNA structures in the human transcriptome beyond evolutionarily conserved regions
RNA structure has been increasingly recognized as a critical player in the biogenesis and turnover of many transcripts classes. In eukaryotes, the prediction of RNA structure by thermodynamic modeling meets fundamental limitations due to the large sizes and complex, discontinuous organization of euk...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
PeerJ Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10691357/ https://www.ncbi.nlm.nih.gov/pubmed/38047033 http://dx.doi.org/10.7717/peerj.16414 |
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author | Margasyuk, Sergey Zavileyskiy, Lev Cao, Changchang Pervouchine, Dmitri |
author_facet | Margasyuk, Sergey Zavileyskiy, Lev Cao, Changchang Pervouchine, Dmitri |
author_sort | Margasyuk, Sergey |
collection | PubMed |
description | RNA structure has been increasingly recognized as a critical player in the biogenesis and turnover of many transcripts classes. In eukaryotes, the prediction of RNA structure by thermodynamic modeling meets fundamental limitations due to the large sizes and complex, discontinuous organization of eukaryotic genes. Signatures of functional RNA structures can be found by detecting compensatory substitutions in homologous sequences, but a comparative approach is applicable only within conserved sequence blocks. Here, we developed a computational pipeline called PHRIC, which is not limited to conserved regions and relies on RNA contacts derived from RNA in situ conformation sequencing (RIC-seq) experiments. It extracts pairs of short RNA fragments surrounded by nested clusters of RNA contacts and predicts long, nearly perfect complementary base pairings formed between these fragments. In application to a panel of RIC-seq experiments in seven human cell lines, PHRIC predicted ~12,000 stable long-range RNA structures with equilibrium free energy below −15 kcal/mol, the vast majority of which fall outside of regions annotated as conserved among vertebrates. These structures, nevertheless, show some level of sequence conservation and remarkable compensatory substitution patterns in other clades. Furthermore, we found that introns have a higher propensity to form stable long-range RNA structures between each other, and moreover that RNA structures tend to concentrate within the same intron rather than connect adjacent introns. These results for the first time extend the application of proximity ligation assays to RNA structure prediction beyond conserved regions. |
format | Online Article Text |
id | pubmed-10691357 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | PeerJ Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-106913572023-12-02 Long-range RNA structures in the human transcriptome beyond evolutionarily conserved regions Margasyuk, Sergey Zavileyskiy, Lev Cao, Changchang Pervouchine, Dmitri PeerJ Bioinformatics RNA structure has been increasingly recognized as a critical player in the biogenesis and turnover of many transcripts classes. In eukaryotes, the prediction of RNA structure by thermodynamic modeling meets fundamental limitations due to the large sizes and complex, discontinuous organization of eukaryotic genes. Signatures of functional RNA structures can be found by detecting compensatory substitutions in homologous sequences, but a comparative approach is applicable only within conserved sequence blocks. Here, we developed a computational pipeline called PHRIC, which is not limited to conserved regions and relies on RNA contacts derived from RNA in situ conformation sequencing (RIC-seq) experiments. It extracts pairs of short RNA fragments surrounded by nested clusters of RNA contacts and predicts long, nearly perfect complementary base pairings formed between these fragments. In application to a panel of RIC-seq experiments in seven human cell lines, PHRIC predicted ~12,000 stable long-range RNA structures with equilibrium free energy below −15 kcal/mol, the vast majority of which fall outside of regions annotated as conserved among vertebrates. These structures, nevertheless, show some level of sequence conservation and remarkable compensatory substitution patterns in other clades. Furthermore, we found that introns have a higher propensity to form stable long-range RNA structures between each other, and moreover that RNA structures tend to concentrate within the same intron rather than connect adjacent introns. These results for the first time extend the application of proximity ligation assays to RNA structure prediction beyond conserved regions. PeerJ Inc. 2023-11-28 /pmc/articles/PMC10691357/ /pubmed/38047033 http://dx.doi.org/10.7717/peerj.16414 Text en © 2023 Margasyuk et al. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits using, remixing, and building upon the work non-commercially, as long as it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. |
spellingShingle | Bioinformatics Margasyuk, Sergey Zavileyskiy, Lev Cao, Changchang Pervouchine, Dmitri Long-range RNA structures in the human transcriptome beyond evolutionarily conserved regions |
title | Long-range RNA structures in the human transcriptome beyond evolutionarily conserved regions |
title_full | Long-range RNA structures in the human transcriptome beyond evolutionarily conserved regions |
title_fullStr | Long-range RNA structures in the human transcriptome beyond evolutionarily conserved regions |
title_full_unstemmed | Long-range RNA structures in the human transcriptome beyond evolutionarily conserved regions |
title_short | Long-range RNA structures in the human transcriptome beyond evolutionarily conserved regions |
title_sort | long-range rna structures in the human transcriptome beyond evolutionarily conserved regions |
topic | Bioinformatics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10691357/ https://www.ncbi.nlm.nih.gov/pubmed/38047033 http://dx.doi.org/10.7717/peerj.16414 |
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