MicroRNA-deficient mouse embryonic stem cells acquire a functional interferon response
When mammalian cells detect a viral infection, they initiate a type I interferon (IFNs) response as part of their innate immune system. This antiviral mechanism is conserved in virtually all cell types, except for embryonic stem cells (ESCs) and oocytes which are intrinsically incapable of producing...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-04-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/44171 |
| _version_ | 1818028512774193152 |
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| author | Jeroen Witteveldt Lisanne I Knol Sara Macias |
| author_facet | Jeroen Witteveldt Lisanne I Knol Sara Macias |
| author_sort | Jeroen Witteveldt |
| collection | DOAJ |
| description | When mammalian cells detect a viral infection, they initiate a type I interferon (IFNs) response as part of their innate immune system. This antiviral mechanism is conserved in virtually all cell types, except for embryonic stem cells (ESCs) and oocytes which are intrinsically incapable of producing IFNs. Despite the importance of the IFN response to fight viral infections, the mechanisms regulating this pathway during pluripotency are still unknown. Here we show that, in the absence of miRNAs, ESCs acquire an active IFN response. Proteomic analysis identified MAVS, a central component of the IFN pathway, to be actively silenced by miRNAs and responsible for suppressing IFN expression in ESCs. Furthermore, we show that knocking out a single miRNA, miR-673, restores the antiviral response in ESCs through MAVS regulation. Our findings suggest that the interaction between miR-673 and MAVS acts as a switch to suppress the antiviral IFN during pluripotency and present genetic approaches to enhance their antiviral immunity. |
| first_indexed | 2024-12-10T05:04:59Z |
| format | Article |
| id | doaj.art-56d2ed11b02a49d384bce6fcb5b05e07 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T05:04:59Z |
| publishDate | 2019-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-56d2ed11b02a49d384bce6fcb5b05e072022-12-22T02:01:17ZengeLife Sciences Publications LtdeLife2050-084X2019-04-01810.7554/eLife.44171MicroRNA-deficient mouse embryonic stem cells acquire a functional interferon responseJeroen Witteveldt0https://orcid.org/0000-0001-8247-7010Lisanne I Knol1https://orcid.org/0000-0002-8975-0398Sara Macias2https://orcid.org/0000-0002-0643-3494Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United KingdomInstitute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United KingdomInstitute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United KingdomWhen mammalian cells detect a viral infection, they initiate a type I interferon (IFNs) response as part of their innate immune system. This antiviral mechanism is conserved in virtually all cell types, except for embryonic stem cells (ESCs) and oocytes which are intrinsically incapable of producing IFNs. Despite the importance of the IFN response to fight viral infections, the mechanisms regulating this pathway during pluripotency are still unknown. Here we show that, in the absence of miRNAs, ESCs acquire an active IFN response. Proteomic analysis identified MAVS, a central component of the IFN pathway, to be actively silenced by miRNAs and responsible for suppressing IFN expression in ESCs. Furthermore, we show that knocking out a single miRNA, miR-673, restores the antiviral response in ESCs through MAVS regulation. Our findings suggest that the interaction between miR-673 and MAVS acts as a switch to suppress the antiviral IFN during pluripotency and present genetic approaches to enhance their antiviral immunity.https://elifesciences.org/articles/44171miRNAantiviralinterferonmicroprocessordicermavs |
| spellingShingle | Jeroen Witteveldt Lisanne I Knol Sara Macias MicroRNA-deficient mouse embryonic stem cells acquire a functional interferon response eLife miRNA antiviral interferon microprocessor dicer mavs |
| title | MicroRNA-deficient mouse embryonic stem cells acquire a functional interferon response |
| title_full | MicroRNA-deficient mouse embryonic stem cells acquire a functional interferon response |
| title_fullStr | MicroRNA-deficient mouse embryonic stem cells acquire a functional interferon response |
| title_full_unstemmed | MicroRNA-deficient mouse embryonic stem cells acquire a functional interferon response |
| title_short | MicroRNA-deficient mouse embryonic stem cells acquire a functional interferon response |
| title_sort | microrna deficient mouse embryonic stem cells acquire a functional interferon response |
| topic | miRNA antiviral interferon microprocessor dicer mavs |
| url | https://elifesciences.org/articles/44171 |
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