Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting
The SARS-CoV-2 virus is a recently-emerged zoonotic pathogen already well adapted to transmission and replication in humans. Although the mutation rate is limited, recently introduced mutations in SARS-CoV-2 have the potential to alter viral fitness. In addition to amino acid changes, mutations coul...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-07-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/13/4807 |
| _version_ | 1797563076379148288 |
|---|---|
| author | Ali Hosseini Rad SM Alexander D. McLellan |
| author_facet | Ali Hosseini Rad SM Alexander D. McLellan |
| author_sort | Ali Hosseini Rad SM |
| collection | DOAJ |
| description | The SARS-CoV-2 virus is a recently-emerged zoonotic pathogen already well adapted to transmission and replication in humans. Although the mutation rate is limited, recently introduced mutations in SARS-CoV-2 have the potential to alter viral fitness. In addition to amino acid changes, mutations could affect RNA secondary structure critical to viral life cycle, or interfere with sequences targeted by host miRNAs. We have analysed subsets of genomes from SARS-CoV-2 isolates from around the globe and show that several mutations introduce changes in Watson–Crick pairing, with resultant changes in predicted secondary structure. Filtering to targets matching miRNAs expressed in SARS-CoV-2-permissive host cells, we identified ten separate target sequences in the SARS-CoV-2 genome; three of these targets have been lost through conserved mutations. A genomic site targeted by the highly abundant miR-197-5p, overexpressed in patients with cardiovascular disease, is lost by a conserved mutation. Our results are compatible with a model that SARS-CoV-2 replication within the human host is constrained by host miRNA defences. The impact of these and further mutations on secondary structures, miRNA targets or potential splice sites offers a new context in which to view future SARS-CoV-2 evolution, and a potential platform for engineering conditional attenuation to vaccine development, as well as providing a better understanding of viral tropism and pathogenesis. |
| first_indexed | 2024-03-10T18:37:26Z |
| format | Article |
| id | doaj.art-5afcee4567f845af8b827f33a0e8dd74 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:37:26Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5afcee4567f845af8b827f33a0e8dd742023-11-20T06:04:48ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-012113480710.3390/ijms21134807Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA TargetingAli Hosseini Rad SM0Alexander D. McLellan1Department of Microbiology and Immunology, University of Otago, Dunedin 9010, Otago, New ZealandDepartment of Microbiology and Immunology, University of Otago, Dunedin 9010, Otago, New ZealandThe SARS-CoV-2 virus is a recently-emerged zoonotic pathogen already well adapted to transmission and replication in humans. Although the mutation rate is limited, recently introduced mutations in SARS-CoV-2 have the potential to alter viral fitness. In addition to amino acid changes, mutations could affect RNA secondary structure critical to viral life cycle, or interfere with sequences targeted by host miRNAs. We have analysed subsets of genomes from SARS-CoV-2 isolates from around the globe and show that several mutations introduce changes in Watson–Crick pairing, with resultant changes in predicted secondary structure. Filtering to targets matching miRNAs expressed in SARS-CoV-2-permissive host cells, we identified ten separate target sequences in the SARS-CoV-2 genome; three of these targets have been lost through conserved mutations. A genomic site targeted by the highly abundant miR-197-5p, overexpressed in patients with cardiovascular disease, is lost by a conserved mutation. Our results are compatible with a model that SARS-CoV-2 replication within the human host is constrained by host miRNA defences. The impact of these and further mutations on secondary structures, miRNA targets or potential splice sites offers a new context in which to view future SARS-CoV-2 evolution, and a potential platform for engineering conditional attenuation to vaccine development, as well as providing a better understanding of viral tropism and pathogenesis.https://www.mdpi.com/1422-0067/21/13/4807SARS-CoV-2RNA secondary structureconserved mutationmiRNA |
| spellingShingle | Ali Hosseini Rad SM Alexander D. McLellan Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting International Journal of Molecular Sciences SARS-CoV-2 RNA secondary structure conserved mutation miRNA |
| title | Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting |
| title_full | Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting |
| title_fullStr | Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting |
| title_full_unstemmed | Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting |
| title_short | Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting |
| title_sort | implications of sars cov 2 mutations for genomic rna structure and host microrna targeting |
| topic | SARS-CoV-2 RNA secondary structure conserved mutation miRNA |
| url | https://www.mdpi.com/1422-0067/21/13/4807 |
| work_keys_str_mv | AT alihosseiniradsm implicationsofsarscov2mutationsforgenomicrnastructureandhostmicrornatargeting AT alexanderdmclellan implicationsofsarscov2mutationsforgenomicrnastructureandhostmicrornatargeting |