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Pervasive RNA folding is crucial for narnavirus genome maintenance
A synthetic biology approach toward constructing an RNA-based genome expands our understanding of living things and opens avenues for technological advancement. For the precise design of an artificial RNA replicon either from scratch or based on a natural RNA replicon, understanding structure–functi...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10293807/ https://www.ncbi.nlm.nih.gov/pubmed/37339222 http://dx.doi.org/10.1073/pnas.2304082120 |
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author | Fukuda, Makiha Cai, Jitong Bader, Joel S. Boeke, Jef D. |
author_facet | Fukuda, Makiha Cai, Jitong Bader, Joel S. Boeke, Jef D. |
author_sort | Fukuda, Makiha |
collection | PubMed |
description | A synthetic biology approach toward constructing an RNA-based genome expands our understanding of living things and opens avenues for technological advancement. For the precise design of an artificial RNA replicon either from scratch or based on a natural RNA replicon, understanding structure–function relationships of RNA sequences is critical. However, our knowledge remains limited to a few particular structural elements intensively studied so far. Here, we conducted a series of site-directed mutagenesis studies of yeast narnaviruses ScNV20S and ScNV23S, perhaps the simplest natural autonomous RNA replicons, to identify RNA elements required for maintenance and replication. RNA structure disruption corresponding to various portions of the entire narnavirus genome suggests that pervasive RNA folding, in addition to the precise secondary structure of genome termini, is essential for maintenance of the RNA replicon in vivo. Computational RNA structure analyses suggest that this scenario likely applies to other “narna-like" viruses. This finding implies selective pressure on these simplest autonomous natural RNA replicons to fold into a unique structure that acquires both thermodynamic and biological stability. We propose the importance of pervasive RNA folding for the design of RNA replicons that could serve as a platform for in vivo continuous evolution as well as an interesting model to study the origin of life. |
format | Online Article Text |
id | pubmed-10293807 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-102938072023-06-28 Pervasive RNA folding is crucial for narnavirus genome maintenance Fukuda, Makiha Cai, Jitong Bader, Joel S. Boeke, Jef D. Proc Natl Acad Sci U S A Biological Sciences A synthetic biology approach toward constructing an RNA-based genome expands our understanding of living things and opens avenues for technological advancement. For the precise design of an artificial RNA replicon either from scratch or based on a natural RNA replicon, understanding structure–function relationships of RNA sequences is critical. However, our knowledge remains limited to a few particular structural elements intensively studied so far. Here, we conducted a series of site-directed mutagenesis studies of yeast narnaviruses ScNV20S and ScNV23S, perhaps the simplest natural autonomous RNA replicons, to identify RNA elements required for maintenance and replication. RNA structure disruption corresponding to various portions of the entire narnavirus genome suggests that pervasive RNA folding, in addition to the precise secondary structure of genome termini, is essential for maintenance of the RNA replicon in vivo. Computational RNA structure analyses suggest that this scenario likely applies to other “narna-like" viruses. This finding implies selective pressure on these simplest autonomous natural RNA replicons to fold into a unique structure that acquires both thermodynamic and biological stability. We propose the importance of pervasive RNA folding for the design of RNA replicons that could serve as a platform for in vivo continuous evolution as well as an interesting model to study the origin of life. National Academy of Sciences 2023-06-20 2023-06-27 /pmc/articles/PMC10293807/ /pubmed/37339222 http://dx.doi.org/10.1073/pnas.2304082120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Fukuda, Makiha Cai, Jitong Bader, Joel S. Boeke, Jef D. Pervasive RNA folding is crucial for narnavirus genome maintenance |
title | Pervasive RNA folding is crucial for narnavirus genome maintenance |
title_full | Pervasive RNA folding is crucial for narnavirus genome maintenance |
title_fullStr | Pervasive RNA folding is crucial for narnavirus genome maintenance |
title_full_unstemmed | Pervasive RNA folding is crucial for narnavirus genome maintenance |
title_short | Pervasive RNA folding is crucial for narnavirus genome maintenance |
title_sort | pervasive rna folding is crucial for narnavirus genome maintenance |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10293807/ https://www.ncbi.nlm.nih.gov/pubmed/37339222 http://dx.doi.org/10.1073/pnas.2304082120 |
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