| First Author | Xi J | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 4 | Pages | 113998 |
| PubMed ID | 38551960 | Mgi Jnum | J:349727 |
| Mgi Id | MGI:7627915 | Doi | 10.1016/j.celrep.2024.113998 |
| Citation | Xi J, et al. (2024) Initiation of a ZAKalpha-dependent ribotoxic stress response by the innate immunity endoribonuclease RNase L. Cell Rep 43(4):113998 |
| abstractText | RNase L is an endoribonuclease of higher vertebrates that functions in antiviral innate immunity. Interferons induce oligoadenylate synthetase enzymes that sense double-stranded RNA of viral origin leading to the synthesis of 2',5'-oligoadenylate (2-5A) activators of RNase L. However, it is unknown precisely how RNase L remodels the host cell transcriptome. To isolate effects of RNase L from other effects of double-stranded RNA or virus, 2-5A is directly introduced into cells. Here, we report that RNase L activation by 2-5A causes a ribotoxic stress response involving the MAP kinase kinase kinase (MAP3K) ZAKalpha, MAP2Ks, and the stress-activated protein kinases JNK and p38alpha. RNase L activation profoundly alters the transcriptome by widespread depletion of mRNAs associated with different cellular functions but also by JNK/p38alpha-stimulated induction of inflammatory genes. These results show that the 2-5A/RNase L system triggers a protein kinase cascade leading to proinflammatory signaling and apoptosis. |
