Modulation of Viral Programmed Ribosomal Frameshifting and Stop Codon Readthrough by the Host Restriction Factor Shiftless
| Autor: | Ian Brierley, Chris H. Hill, Sawsan Napthine, Holly C. M. Nugent |
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| Přispěvatelé: | Napthine, Sawsan [0000-0001-7404-8494], Brierley, Ian [0000-0003-3965-4370], Apollo - University of Cambridge Repository |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Gene Expression Regulation Viral viruses RNA-binding protein virus Virus Replication Ribosome Microbiology Article frameshift 03 medical and health sciences Viral Proteins Virology Murine leukemia virus Escherichia coli Humans Gene Translational frameshift 030102 biochemistry & molecular biology biology Base Sequence Chemistry RNA Frameshifting Ribosomal RNA-Binding Proteins biology.organism_classification Stop codon QR1-502 Cell biology Coronavirus Leukemia Virus Murine 030104 developmental biology Infectious Diseases RNA Recognition Motif Proteins Viral replication ribosome readthrough Codon Terminator RNA Viral Shiftless |
| Zdroj: | Viruses, Vol 13, Iss 1230, p 1230 (2021) Viruses Volume 13 Issue 7 |
| ISSN: | 1999-4915 |
| Popis: | The product of the interferon-stimulated gene C19orf66, Shiftless (SHFL), restricts human immunodeficiency virus replication through downregulation of the efficiency of the viral gag/pol frameshifting signal. In this study, we demonstrate that bacterially expressed, purified SHFL can decrease the efficiency of programmed ribosomal frameshifting in vitro at a variety of sites, including the RNA pseudoknot-dependent signals of the coronaviruses IBV, SARS-CoV and SARS-CoV-2, and the protein-dependent stimulators of the cardioviruses EMCV and TMEV. SHFL also reduced the efficiency of stop-codon readthrough at the murine leukemia virus gag/pol signal. Using size-exclusion chromatography, we confirm the binding of the purified protein to mammalian ribosomes in vitro. Finally, through electrophoretic mobility shift assays and mutational analysis, we show that expressed SHFL has strong RNA binding activity that is necessary for full activity in the inhibition of frameshifting, but shows no clear specificity for stimulatory RNA structures. |
| Databáze: | OpenAIRE |
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