Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting.
Identifieur interne : 000059 ( Main/Corpus ); précédent : 000058; suivant : 000060Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting.
Auteurs : Ali Hosseini Rad Sm ; Alexander D. MclellanSource :
- International journal of molecular sciences [ 1422-0067 ] ; 2020.
English descriptors
- KwdEn :
- 3' Untranslated Regions (MeSH), Base Sequence (MeSH), Betacoronavirus (genetics), Coronavirus Infections (pathology), Coronavirus Infections (virology), Databases, Genetic (MeSH), Genome, Viral (MeSH), Humans (MeSH), MicroRNAs (chemistry), MicroRNAs (genetics), MicroRNAs (metabolism), Mutation (MeSH), Nucleic Acid Conformation (MeSH), Pandemics (MeSH), Pneumonia, Viral (pathology), Pneumonia, Viral (virology), RNA Splice Sites (MeSH), RNA Splicing (MeSH), RNA, Viral (chemistry), Sequence Alignment (MeSH), Viral Nonstructural Proteins (genetics), Viral Proteins (chemistry), Viral Proteins (genetics), Viral Proteins (metabolism).
- MESH :
- chemical , chemistry : MicroRNAs, RNA, Viral, Viral Proteins.
- chemical , genetics : MicroRNAs, Viral Nonstructural Proteins, Viral Proteins.
- chemical , metabolism : MicroRNAs, Viral Proteins.
- chemical : 3' Untranslated Regions, RNA Splice Sites.
- genetics : Betacoronavirus.
- pathology : Coronavirus Infections, Pneumonia, Viral.
- virology : Coronavirus Infections, Pneumonia, Viral.
- Base Sequence, Databases, Genetic, Genome, Viral, Humans, Mutation, Nucleic Acid Conformation, Pandemics, RNA Splicing, Sequence Alignment.
Abstract
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.
DOI: 10.3390/ijms21134807
PubMed: 32645951
Links to Exploration step
pubmed:32645951Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting.</title><author><name sortKey="Hosseini Rad Sm, Ali" sort="Hosseini Rad Sm, Ali" uniqKey="Hosseini Rad Sm A" first="Ali" last="Hosseini Rad Sm">Ali Hosseini Rad Sm</name><affiliation><nlm:affiliation>Department of Microbiology and Immunology, University of Otago, Dunedin 9010, Otago, New Zealand.</nlm:affiliation></affiliation></author><author><name sortKey="Mclellan, Alexander D" sort="Mclellan, Alexander D" uniqKey="Mclellan A" first="Alexander D" last="Mclellan">Alexander D. Mclellan</name><affiliation><nlm:affiliation>Department of Microbiology and Immunology, University of Otago, Dunedin 9010, Otago, New Zealand.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32645951</idno><idno type="pmid">32645951</idno><idno type="doi">10.3390/ijms21134807</idno><idno type="wicri:Area/Main/Corpus">000059</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000059</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting.</title><author><name sortKey="Hosseini Rad Sm, Ali" sort="Hosseini Rad Sm, Ali" uniqKey="Hosseini Rad Sm A" first="Ali" last="Hosseini Rad Sm">Ali Hosseini Rad Sm</name><affiliation><nlm:affiliation>Department of Microbiology and Immunology, University of Otago, Dunedin 9010, Otago, New Zealand.</nlm:affiliation></affiliation></author><author><name sortKey="Mclellan, Alexander D" sort="Mclellan, Alexander D" uniqKey="Mclellan A" first="Alexander D" last="Mclellan">Alexander D. Mclellan</name><affiliation><nlm:affiliation>Department of Microbiology and Immunology, University of Otago, Dunedin 9010, Otago, New Zealand.</nlm:affiliation></affiliation></author></analytic><series><title level="j">International journal of molecular sciences</title><idno type="eISSN">1422-0067</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>3' Untranslated Regions (MeSH)</term><term>Base Sequence (MeSH)</term><term>Betacoronavirus (genetics)</term><term>Coronavirus Infections (pathology)</term><term>Coronavirus Infections (virology)</term><term>Databases, Genetic (MeSH)</term><term>Genome, Viral (MeSH)</term><term>Humans (MeSH)</term><term>MicroRNAs (chemistry)</term><term>MicroRNAs (genetics)</term><term>MicroRNAs (metabolism)</term><term>Mutation (MeSH)</term><term>Nucleic Acid Conformation (MeSH)</term><term>Pandemics (MeSH)</term><term>Pneumonia, Viral (pathology)</term><term>Pneumonia, Viral (virology)</term><term>RNA Splice Sites (MeSH)</term><term>RNA Splicing (MeSH)</term><term>RNA, Viral (chemistry)</term><term>Sequence Alignment (MeSH)</term><term>Viral Nonstructural Proteins (genetics)</term><term>Viral Proteins (chemistry)</term><term>Viral Proteins (genetics)</term><term>Viral Proteins (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>MicroRNAs</term><term>RNA, Viral</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>MicroRNAs</term><term>Viral Nonstructural Proteins</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>MicroRNAs</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>3' Untranslated Regions</term><term>RNA Splice Sites</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Betacoronavirus</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Coronavirus Infections</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Base Sequence</term><term>Databases, Genetic</term><term>Genome, Viral</term><term>Humans</term><term>Mutation</term><term>Nucleic Acid Conformation</term><term>Pandemics</term><term>RNA Splicing</term><term>Sequence Alignment</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32645951</PMID><DateCompleted><Year>2020</Year><Month>07</Month><Day>16</Day></DateCompleted><DateRevised><Year>2020</Year><Month>07</Month><Day>16</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1422-0067</ISSN><JournalIssue CitedMedium="Internet"><Volume>21</Volume><Issue>13</Issue><PubDate><Year>2020</Year><Month>Jul</Month><Day>07</Day></PubDate></JournalIssue><Title>International journal of molecular sciences</Title><ISOAbbreviation>Int J Mol Sci</ISOAbbreviation></Journal><ArticleTitle>Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">E4807</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.3390/ijms21134807</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Hosseini Rad Sm</LastName><ForeName>Ali</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Otago, Dunedin 9010, Otago, New Zealand.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McLellan</LastName><ForeName>Alexander D</ForeName><Initials>AD</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Otago, Dunedin 9010, Otago, New Zealand.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>07</Month><Day>07</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Int J Mol Sci</MedlineTA><NlmUniqueID>101092791</NlmUniqueID><ISSNLinking>1422-0067</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D020413">3' Untranslated Regions</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D035683">MicroRNAs</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D022821">RNA Splice Sites</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D012367">RNA, 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