PKR and TLR3 trigger distinct signals that coordinate the induction of antiviral apoptosis
Abstract RIG-I-like receptors (RLRs), protein kinase R (PKR), and endosomal Toll-like receptor 3 (TLR3) sense viral non-self RNA and are involved in cell fate determination. However, the mechanisms by which intracellular RNA induces apoptosis, particularly the role of each RNA sensor, remain unclear...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-08-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-05101-3 |
| _version_ | 1811340431338766336 |
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| author | Wenjie Zuo Mai Wakimoto Noriyasu Kozaiwa Yutaro Shirasaka Seong-Wook Oh Shiori Fujiwara Hitoshi Miyachi Amane Kogure Hiroki Kato Takashi Fujita |
| author_facet | Wenjie Zuo Mai Wakimoto Noriyasu Kozaiwa Yutaro Shirasaka Seong-Wook Oh Shiori Fujiwara Hitoshi Miyachi Amane Kogure Hiroki Kato Takashi Fujita |
| author_sort | Wenjie Zuo |
| collection | DOAJ |
| description | Abstract RIG-I-like receptors (RLRs), protein kinase R (PKR), and endosomal Toll-like receptor 3 (TLR3) sense viral non-self RNA and are involved in cell fate determination. However, the mechanisms by which intracellular RNA induces apoptosis, particularly the role of each RNA sensor, remain unclear. We performed cytoplasmic injections of different types of RNA and elucidated the molecular mechanisms underlying viral dsRNA-induced apoptosis. The results obtained revealed that short 5′-triphosphate dsRNA, the sole ligand of RIG-I, induced slow apoptosis in a fraction of cells depending on IRF-3 transcriptional activity and IFN-I production. However, intracellular long dsRNA was sensed by PKR and TLR3, which activate distinct signals, and synergistically induced rapid apoptosis. PKR essentially induced translational arrest, resulting in reduced levels of cellular FLICE-like inhibitory protein and functioned in the TLR3/TRIF-dependent activation of caspase 8. The present results demonstrated that PKR and TLR3 were both essential for inducing the viral RNA-mediated apoptosis of infected cells and the arrest of viral production. |
| first_indexed | 2024-04-13T18:41:51Z |
| format | Article |
| id | doaj.art-b6b843f8f2454132a6699e02d5be8df0 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-13T18:41:51Z |
| publishDate | 2022-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-b6b843f8f2454132a6699e02d5be8df02022-12-22T02:34:42ZengNature Publishing GroupCell Death and Disease2041-48892022-08-0113811510.1038/s41419-022-05101-3PKR and TLR3 trigger distinct signals that coordinate the induction of antiviral apoptosisWenjie Zuo0Mai Wakimoto1Noriyasu Kozaiwa2Yutaro Shirasaka3Seong-Wook Oh4Shiori Fujiwara5Hitoshi Miyachi6Amane Kogure7Hiroki Kato8Takashi Fujita9Division of Integrated Life Science, Graduate School of Biostudies, Kyoto UniversityDivision of Integrated Life Science, Graduate School of Biostudies, Kyoto UniversityDivision of Integrated Life Science, Graduate School of Biostudies, Kyoto UniversityDivision of Integrated Life Science, Graduate School of Biostudies, Kyoto UniversityLaboratory of Regulatory Information, Institute for Frontier Life and Medical Science, Kyoto UniversityDivision of Integrated Life Science, Graduate School of Biostudies, Kyoto UniversityInstitute for Virus Research, Kyoto UniversityLaboratory of Regulatory Information, Institute for Frontier Life and Medical Science, Kyoto UniversityInstitute for Cardiovascular Immunology, University Hospital BonnDivision of Integrated Life Science, Graduate School of Biostudies, Kyoto UniversityAbstract RIG-I-like receptors (RLRs), protein kinase R (PKR), and endosomal Toll-like receptor 3 (TLR3) sense viral non-self RNA and are involved in cell fate determination. However, the mechanisms by which intracellular RNA induces apoptosis, particularly the role of each RNA sensor, remain unclear. We performed cytoplasmic injections of different types of RNA and elucidated the molecular mechanisms underlying viral dsRNA-induced apoptosis. The results obtained revealed that short 5′-triphosphate dsRNA, the sole ligand of RIG-I, induced slow apoptosis in a fraction of cells depending on IRF-3 transcriptional activity and IFN-I production. However, intracellular long dsRNA was sensed by PKR and TLR3, which activate distinct signals, and synergistically induced rapid apoptosis. PKR essentially induced translational arrest, resulting in reduced levels of cellular FLICE-like inhibitory protein and functioned in the TLR3/TRIF-dependent activation of caspase 8. The present results demonstrated that PKR and TLR3 were both essential for inducing the viral RNA-mediated apoptosis of infected cells and the arrest of viral production.https://doi.org/10.1038/s41419-022-05101-3 |
| spellingShingle | Wenjie Zuo Mai Wakimoto Noriyasu Kozaiwa Yutaro Shirasaka Seong-Wook Oh Shiori Fujiwara Hitoshi Miyachi Amane Kogure Hiroki Kato Takashi Fujita PKR and TLR3 trigger distinct signals that coordinate the induction of antiviral apoptosis Cell Death and Disease |
| title | PKR and TLR3 trigger distinct signals that coordinate the induction of antiviral apoptosis |
| title_full | PKR and TLR3 trigger distinct signals that coordinate the induction of antiviral apoptosis |
| title_fullStr | PKR and TLR3 trigger distinct signals that coordinate the induction of antiviral apoptosis |
| title_full_unstemmed | PKR and TLR3 trigger distinct signals that coordinate the induction of antiviral apoptosis |
| title_short | PKR and TLR3 trigger distinct signals that coordinate the induction of antiviral apoptosis |
| title_sort | pkr and tlr3 trigger distinct signals that coordinate the induction of antiviral apoptosis |
| url | https://doi.org/10.1038/s41419-022-05101-3 |
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