RNA-seq analyses reveal the relevance of RNAs involved in ribosomal complex to induce mammalian prion protein aggregation and phase separation in vitro
Conformational conversion of cellular prion protein (PrPC) into infectious PrP (PrPSc) is one of the most intriguing processes in modern Biology. It is well accepted that this transition is catalysed by one or more cofactors that lower the energy barrier between the different PrP forms. Among potent...
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| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | RNA Biology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/15476286.2025.2508107 |
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| author | Ana C. Tahira Mariana P. B. Gomes Maria Heloisa Freire Marcelly Muxfeldt Francisco Prosdocimi Yulli M. Passos Murilo Sena Amaral Leticia P. Felix Valadão Luciana P. Rangel Jerson L. Silva Sergio Verjovski-Almeida Yraima Cordeiro |
| author_facet | Ana C. Tahira Mariana P. B. Gomes Maria Heloisa Freire Marcelly Muxfeldt Francisco Prosdocimi Yulli M. Passos Murilo Sena Amaral Leticia P. Felix Valadão Luciana P. Rangel Jerson L. Silva Sergio Verjovski-Almeida Yraima Cordeiro |
| author_sort | Ana C. Tahira |
| collection | DOAJ |
| description | Conformational conversion of cellular prion protein (PrPC) into infectious PrP (PrPSc) is one of the most intriguing processes in modern Biology. It is well accepted that this transition is catalysed by one or more cofactors that lower the energy barrier between the different PrP forms. Among potential candidates, RNA molecules are strong contenders. Our group has pursued nucleic acids, both DNA and RNA, capable of inducing PrP misfolding, aggregation, and, more recently, phase separation, a process proposed to precede aggregation in degenerative disorders. We found that the interaction between recombinant PrP (rPrP) and total RNA extracted from neuroblastoma cells (N2aRNA) results in significant structural alterations. Here, we use rPrP:N2aRNA as a model to search for RNAs capable of inducing full-length murine rPrP phase separation and/or aggregation. N2aRNA was incubated with rPrP and after that, RNA-seq analysis was conducted with RNAs isolated from the insoluble material using two different protocols. We analysed thousands of RNA-seq reads, most of which represented ribosomal RNA molecules. The set of recovered molecules is heterogeneous; nevertheless, three low-complexity consensus motifs within the sequences of RNAs involved in ribosomal complex were identified as significantly enriched in the RNAs bound to rPrP, suggesting that a population of RNAs is responsible for inducing PrP phase transitions. We hypothesize that RNA transcripts enriched in a set of low complexity motif sequences with predicted structural similarities can be involved in PrPC binding. This interaction would lead to phase separation and, ultimately, result in aggregation into scrapie-like species, in a stoichiometry-dependent manner. |
| format | Article |
| id | doaj-art-bf3b8cd2a16b4adfad3b5ddd383c8045 |
| institution | OA Journals |
| issn | 1547-6286 1555-8584 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | RNA Biology |
| spelling | doaj-art-bf3b8cd2a16b4adfad3b5ddd383c80452025-08-20T02:17:01ZengTaylor & Francis GroupRNA Biology1547-62861555-85842025-12-0122111610.1080/15476286.2025.2508107RNA-seq analyses reveal the relevance of RNAs involved in ribosomal complex to induce mammalian prion protein aggregation and phase separation in vitroAna C. Tahira0Mariana P. B. Gomes1Maria Heloisa Freire2Marcelly Muxfeldt3Francisco Prosdocimi4Yulli M. Passos5Murilo Sena Amaral6Leticia P. Felix Valadão7Luciana P. Rangel8Jerson L. Silva9Sergio Verjovski-Almeida10Yraima Cordeiro11Laboratório de Ciclo Celular, Instituto Butantan, São Paulo, BrasilFaculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrasilFaculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrasilFaculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrasilInstituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrasilFaculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrasilLaboratório de Ciclo Celular, Instituto Butantan, São Paulo, BrasilFaculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrasilFaculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrasilInstituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrasilLaboratório de Ciclo Celular, Instituto Butantan, São Paulo, BrasilFaculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrasilConformational conversion of cellular prion protein (PrPC) into infectious PrP (PrPSc) is one of the most intriguing processes in modern Biology. It is well accepted that this transition is catalysed by one or more cofactors that lower the energy barrier between the different PrP forms. Among potential candidates, RNA molecules are strong contenders. Our group has pursued nucleic acids, both DNA and RNA, capable of inducing PrP misfolding, aggregation, and, more recently, phase separation, a process proposed to precede aggregation in degenerative disorders. We found that the interaction between recombinant PrP (rPrP) and total RNA extracted from neuroblastoma cells (N2aRNA) results in significant structural alterations. Here, we use rPrP:N2aRNA as a model to search for RNAs capable of inducing full-length murine rPrP phase separation and/or aggregation. N2aRNA was incubated with rPrP and after that, RNA-seq analysis was conducted with RNAs isolated from the insoluble material using two different protocols. We analysed thousands of RNA-seq reads, most of which represented ribosomal RNA molecules. The set of recovered molecules is heterogeneous; nevertheless, three low-complexity consensus motifs within the sequences of RNAs involved in ribosomal complex were identified as significantly enriched in the RNAs bound to rPrP, suggesting that a population of RNAs is responsible for inducing PrP phase transitions. We hypothesize that RNA transcripts enriched in a set of low complexity motif sequences with predicted structural similarities can be involved in PrPC binding. This interaction would lead to phase separation and, ultimately, result in aggregation into scrapie-like species, in a stoichiometry-dependent manner.https://www.tandfonline.com/doi/10.1080/15476286.2025.2508107Prion proteinRNA-seqChIP-seqprion diseasesRNAnucleic acid |
| spellingShingle | Ana C. Tahira Mariana P. B. Gomes Maria Heloisa Freire Marcelly Muxfeldt Francisco Prosdocimi Yulli M. Passos Murilo Sena Amaral Leticia P. Felix Valadão Luciana P. Rangel Jerson L. Silva Sergio Verjovski-Almeida Yraima Cordeiro RNA-seq analyses reveal the relevance of RNAs involved in ribosomal complex to induce mammalian prion protein aggregation and phase separation in vitro RNA Biology Prion protein RNA-seq ChIP-seq prion diseases RNA nucleic acid |
| title | RNA-seq analyses reveal the relevance of RNAs involved in ribosomal complex to induce mammalian prion protein aggregation and phase separation in vitro |
| title_full | RNA-seq analyses reveal the relevance of RNAs involved in ribosomal complex to induce mammalian prion protein aggregation and phase separation in vitro |
| title_fullStr | RNA-seq analyses reveal the relevance of RNAs involved in ribosomal complex to induce mammalian prion protein aggregation and phase separation in vitro |
| title_full_unstemmed | RNA-seq analyses reveal the relevance of RNAs involved in ribosomal complex to induce mammalian prion protein aggregation and phase separation in vitro |
| title_short | RNA-seq analyses reveal the relevance of RNAs involved in ribosomal complex to induce mammalian prion protein aggregation and phase separation in vitro |
| title_sort | rna seq analyses reveal the relevance of rnas involved in ribosomal complex to induce mammalian prion protein aggregation and phase separation in vitro |
| topic | Prion protein RNA-seq ChIP-seq prion diseases RNA nucleic acid |
| url | https://www.tandfonline.com/doi/10.1080/15476286.2025.2508107 |
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