Expression of RNautophagy/DNautophagy-related genes is regulated under control of an innate immune receptor
Double-stranded RNA (dsRNA) is a molecular pattern uniquely produced in cells infected with various viruses as a product or byproduct of replication. Cells detect such molecules, which indicate non-self invasion, and induce diverse immune responses to eliminate them. The degradation of virus-derived...
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Taylor & Francis Group
2024-12-01
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| Series: | RNA Biology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/15476286.2023.2291610 |
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| author | Yuuki Fujiwara Kazuki Oroku Yinping Zhou Masayuki Takahashi Taiichi Katayama Keiji Wada Nobuyuki Tsutsumi Tetsuo Sato Tomohiro Kabuta |
| author_facet | Yuuki Fujiwara Kazuki Oroku Yinping Zhou Masayuki Takahashi Taiichi Katayama Keiji Wada Nobuyuki Tsutsumi Tetsuo Sato Tomohiro Kabuta |
| author_sort | Yuuki Fujiwara |
| collection | DOAJ |
| description | Double-stranded RNA (dsRNA) is a molecular pattern uniquely produced in cells infected with various viruses as a product or byproduct of replication. Cells detect such molecules, which indicate non-self invasion, and induce diverse immune responses to eliminate them. The degradation of virus-derived molecules can also play a role in the removal of pathogens and suppression of their replication. RNautophagy and DNautophagy are cellular degradative pathways in which RNA and DNA are directly imported into a hydrolytic organelle, the lysosome. Two lysosomal membrane proteins, SIDT2 and LAMP2C, mediate nucleic acid uptake via this pathway. Here, we showed that the expression of both SIDT2 and LAMP2C is selectively upregulated during the intracellular detection of poly(I:C), a synthetic analog of dsRNA that mimics viral infection. The upregulation of these two gene products upon poly(I:C) introduction was transient and synchronized. We also observed that the induction of SIDT2 and LAMP2C expression by poly(I:C) was dependent on MDA5, a cytoplasmic innate immune receptor that directly recognizes poly(I:C) and induces various antiviral responses. Finally, we showed that lysosomes can target viral RNA for degradation via RNautophagy and may suppress viral replication. Our results revealed a novel degradative pathway in cells as a downstream component of the innate immune response and provided evidence suggesting that the degradation of viral nucleic acids via RNautophagy/DNautophagy contributes to the suppression of viral replication. |
| format | Article |
| id | doaj-art-cd8de3e058254b16a0306e53b83e5b7a |
| institution | OA Journals |
| issn | 1547-6286 1555-8584 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | RNA Biology |
| spelling | doaj-art-cd8de3e058254b16a0306e53b83e5b7a2025-08-20T02:33:50ZengTaylor & Francis GroupRNA Biology1547-62861555-85842024-12-01211808810.1080/15476286.2023.2291610Expression of RNautophagy/DNautophagy-related genes is regulated under control of an innate immune receptorYuuki Fujiwara0Kazuki Oroku1Yinping Zhou2Masayuki Takahashi3Taiichi Katayama4Keiji Wada5Nobuyuki Tsutsumi6Tetsuo Sato7Tomohiro Kabuta8Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, JapanResearch Department, Nippon Institute for Biological Science, Ome, Tokyo, JapanDepartment of Child Development and Molecular Brain Science, United Graduate School of Child Development, Osaka University, Suita, Osaka, JapanDepartment of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, JapanDepartment of Child Development and Molecular Brain Science, United Graduate School of Child Development, Osaka University, Suita, Osaka, JapanDepartment of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, JapanResearch Department, Nippon Institute for Biological Science, Ome, Tokyo, JapanResearch Department, Nippon Institute for Biological Science, Ome, Tokyo, JapanDepartment of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, JapanDouble-stranded RNA (dsRNA) is a molecular pattern uniquely produced in cells infected with various viruses as a product or byproduct of replication. Cells detect such molecules, which indicate non-self invasion, and induce diverse immune responses to eliminate them. The degradation of virus-derived molecules can also play a role in the removal of pathogens and suppression of their replication. RNautophagy and DNautophagy are cellular degradative pathways in which RNA and DNA are directly imported into a hydrolytic organelle, the lysosome. Two lysosomal membrane proteins, SIDT2 and LAMP2C, mediate nucleic acid uptake via this pathway. Here, we showed that the expression of both SIDT2 and LAMP2C is selectively upregulated during the intracellular detection of poly(I:C), a synthetic analog of dsRNA that mimics viral infection. The upregulation of these two gene products upon poly(I:C) introduction was transient and synchronized. We also observed that the induction of SIDT2 and LAMP2C expression by poly(I:C) was dependent on MDA5, a cytoplasmic innate immune receptor that directly recognizes poly(I:C) and induces various antiviral responses. Finally, we showed that lysosomes can target viral RNA for degradation via RNautophagy and may suppress viral replication. Our results revealed a novel degradative pathway in cells as a downstream component of the innate immune response and provided evidence suggesting that the degradation of viral nucleic acids via RNautophagy/DNautophagy contributes to the suppression of viral replication.https://www.tandfonline.com/doi/10.1080/15476286.2023.2291610LysosomeRNautophagyDNautophagyPAMPsDouble-stranded RNAPRRs |
| spellingShingle | Yuuki Fujiwara Kazuki Oroku Yinping Zhou Masayuki Takahashi Taiichi Katayama Keiji Wada Nobuyuki Tsutsumi Tetsuo Sato Tomohiro Kabuta Expression of RNautophagy/DNautophagy-related genes is regulated under control of an innate immune receptor RNA Biology Lysosome RNautophagy DNautophagy PAMPs Double-stranded RNA PRRs |
| title | Expression of RNautophagy/DNautophagy-related genes is regulated under control of an innate immune receptor |
| title_full | Expression of RNautophagy/DNautophagy-related genes is regulated under control of an innate immune receptor |
| title_fullStr | Expression of RNautophagy/DNautophagy-related genes is regulated under control of an innate immune receptor |
| title_full_unstemmed | Expression of RNautophagy/DNautophagy-related genes is regulated under control of an innate immune receptor |
| title_short | Expression of RNautophagy/DNautophagy-related genes is regulated under control of an innate immune receptor |
| title_sort | expression of rnautophagy dnautophagy related genes is regulated under control of an innate immune receptor |
| topic | Lysosome RNautophagy DNautophagy PAMPs Double-stranded RNA PRRs |
| url | https://www.tandfonline.com/doi/10.1080/15476286.2023.2291610 |
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