Structural and functional conservation of cis-acting RNA elements in coronavirus 5'-terminal genome regions
| Autor: | Markus Fricke, Nadja Karl, Manja Marz, Kevin Lamkiewicz, Daniel Petersen, John Ziebuhr, Ramakanth Madhugiri, Ulrike C. Wend, Robina Scheuer |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Coronavirus phylogeny Replication Genome Viral Regulatory Sequences Nucleic Acid Biology Virus Replication medicine.disease_cause Genome Article Cell Line 03 medical and health sciences Coronavirus 229E Human Virology medicine Humans cis-acting RNA element Nucleic acid structure RNA structure Coronavirus Genetics Base Sequence virus diseases RNA biology.organism_classification Stem-loop Coronavirus NL63 Human 030104 developmental biology Viral replication Regulatory sequence Nucleic Acid Conformation RNA Viral Betacoronavirus |
| Zdroj: | Virology |
| ISSN: | 0042-6822 |
| Popis: | Structure predictions suggest a partial conservation of RNA structure elements in coronavirus terminal genome regions. Here, we determined the structures of stem-loops (SL) 1 and 2 of two alphacoronaviruses, human coronavirus (HCoV) 229E and NL63, by RNA structure probing and studied the functional relevance of these putative cis-acting elements. HCoV-229E SL1 and SL2 mutants generated by reverse genetics were used to study the effects on viral replication of single-nucleotide substitutions predicted to destabilize the SL1 and SL2 structures. The data provide conclusive evidence for the critical role of SL1 and SL2 in HCoV-229E replication and, in some cases, revealed parallels with previously characterized betacoronavirus SL1 and SL2 elements. Also, we were able to rescue viable HCoV-229E mutants carrying replacements of SL2 with equivalent betacoronavirus structural elements. The data obtained in this study reveal a remarkable degree of structural and functional conservation of 5′-terminal RNA structural elements across coronavirus genus boundaries. Highlights • Conservation of 5'-terminal SL1 and SL2 elements in alpha- and betacoronaviruses. • HCoV-229E reverse genetics data suggest critical role for SL1/2 in viral replication. • Replacement of SL2 in HCoV-229E with betacoronavirus equivalents is tolerated. |
| Databáze: | OpenAIRE |
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