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Mouse Ifit1b is a cap1-RNA–binding protein that inhibits mouse coronavirus translation and is regulated by complexing with Ifit1c

Knockout mouse models have been extensively used to study the antiviral activity of IFIT (interferon-induced protein with tetratricopeptide repeats). Human IFIT1 binds to cap0 (m7GpppN) RNA, which lacks methylation on the first and second cap-proximal nucleotides (cap1, m7GpppNm, and cap2, m7GpppNmN...

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Autores principales: Mears, Harriet V., Sweeney, Trevor R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762956/
https://www.ncbi.nlm.nih.gov/pubmed/33454014
http://dx.doi.org/10.1074/jbc.RA120.014695
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author Mears, Harriet V.
Sweeney, Trevor R.
author_facet Mears, Harriet V.
Sweeney, Trevor R.
author_sort Mears, Harriet V.
collection PubMed
description Knockout mouse models have been extensively used to study the antiviral activity of IFIT (interferon-induced protein with tetratricopeptide repeats). Human IFIT1 binds to cap0 (m7GpppN) RNA, which lacks methylation on the first and second cap-proximal nucleotides (cap1, m7GpppNm, and cap2, m7GpppNmNm, respectively). These modifications are signatures of “self” in higher eukaryotes, whereas unmodified cap0-RNA is recognized as foreign and, therefore, potentially harmful to the host cell. IFIT1 inhibits translation at the initiation stage by competing with the cap-binding initiation factor complex, eIF4F, restricting infection by certain viruses that possess “nonself” cap0-mRNAs. However, in mice and other rodents, the IFIT1 orthologue has been lost, and the closely related Ifit1b has been duplicated twice, yielding three paralogues: Ifit1, Ifit1b, and Ifit1c. Although murine Ifit1 is similar to human IFIT1 in its cap0-RNA–binding selectivity, the roles of Ifit1b and Ifit1c are unknown. Here, we found that Ifit1b preferentially binds to cap1-RNA, whereas binding is much weaker to cap0- and cap2-RNA. In murine cells, we show that Ifit1b can modulate host translation and restrict WT mouse coronavirus infection. We found that Ifit1c acts as a stimulatory cofactor for both Ifit1 and Ifit1b, promoting their translation inhibition. In this way, Ifit1c acts in an analogous fashion to human IFIT3, which is a cofactor to human IFIT1. This work clarifies similarities and differences between the human and murine IFIT families to facilitate better design and interpretation of mouse models of human infection and sheds light on the evolutionary plasticity of the IFIT family.
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spelling pubmed-77629562021-01-07 Mouse Ifit1b is a cap1-RNA–binding protein that inhibits mouse coronavirus translation and is regulated by complexing with Ifit1c Mears, Harriet V. Sweeney, Trevor R. J Biol Chem Immunology Knockout mouse models have been extensively used to study the antiviral activity of IFIT (interferon-induced protein with tetratricopeptide repeats). Human IFIT1 binds to cap0 (m7GpppN) RNA, which lacks methylation on the first and second cap-proximal nucleotides (cap1, m7GpppNm, and cap2, m7GpppNmNm, respectively). These modifications are signatures of “self” in higher eukaryotes, whereas unmodified cap0-RNA is recognized as foreign and, therefore, potentially harmful to the host cell. IFIT1 inhibits translation at the initiation stage by competing with the cap-binding initiation factor complex, eIF4F, restricting infection by certain viruses that possess “nonself” cap0-mRNAs. However, in mice and other rodents, the IFIT1 orthologue has been lost, and the closely related Ifit1b has been duplicated twice, yielding three paralogues: Ifit1, Ifit1b, and Ifit1c. Although murine Ifit1 is similar to human IFIT1 in its cap0-RNA–binding selectivity, the roles of Ifit1b and Ifit1c are unknown. Here, we found that Ifit1b preferentially binds to cap1-RNA, whereas binding is much weaker to cap0- and cap2-RNA. In murine cells, we show that Ifit1b can modulate host translation and restrict WT mouse coronavirus infection. We found that Ifit1c acts as a stimulatory cofactor for both Ifit1 and Ifit1b, promoting their translation inhibition. In this way, Ifit1c acts in an analogous fashion to human IFIT3, which is a cofactor to human IFIT1. This work clarifies similarities and differences between the human and murine IFIT families to facilitate better design and interpretation of mouse models of human infection and sheds light on the evolutionary plasticity of the IFIT family. American Society for Biochemistry and Molecular Biology 2020-12-18 2020-10-19 /pmc/articles/PMC7762956/ /pubmed/33454014 http://dx.doi.org/10.1074/jbc.RA120.014695 Text en © 2020 Mears and Sweeney. Author's Choice—Final version open access under the terms of the Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0) .
spellingShingle Immunology
Mears, Harriet V.
Sweeney, Trevor R.
Mouse Ifit1b is a cap1-RNA–binding protein that inhibits mouse coronavirus translation and is regulated by complexing with Ifit1c
title Mouse Ifit1b is a cap1-RNA–binding protein that inhibits mouse coronavirus translation and is regulated by complexing with Ifit1c
title_full Mouse Ifit1b is a cap1-RNA–binding protein that inhibits mouse coronavirus translation and is regulated by complexing with Ifit1c
title_fullStr Mouse Ifit1b is a cap1-RNA–binding protein that inhibits mouse coronavirus translation and is regulated by complexing with Ifit1c
title_full_unstemmed Mouse Ifit1b is a cap1-RNA–binding protein that inhibits mouse coronavirus translation and is regulated by complexing with Ifit1c
title_short Mouse Ifit1b is a cap1-RNA–binding protein that inhibits mouse coronavirus translation and is regulated by complexing with Ifit1c
title_sort mouse ifit1b is a cap1-rna–binding protein that inhibits mouse coronavirus translation and is regulated by complexing with ifit1c
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762956/
https://www.ncbi.nlm.nih.gov/pubmed/33454014
http://dx.doi.org/10.1074/jbc.RA120.014695
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