{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRNU7-1 encodes the RNA component of the U7 small nuclear ribonucleoprotein (U7 snRNP) complex, which is essential for the proper 3′ end processing of replication-dependent histone pre-mRNAs. Dysfunctional RNU7-1, as observed in certain cases of Aicardi‐Goutiérès syndrome, results in misprocessing of canonical histone transcripts, thereby perturbing the balance of histone proteins integrated into chromatin. This disruption in histone stoichiometry is critical because it undermines chromatin packaging, ultimately facilitating inappropriate access of self-DNA to cytosolic sensors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe aberrant processing of histone pre-mRNAs due to RNU7-1 mutations leads to deficiencies in linker histone incorporation, thereby destabilizing the chromatin structure and exposing nuclear DNA to innate immune sensors. This altered chromatin environment triggers the activation of cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS), which in turn provokes signaling through the stimulator of interferon genes (STING) pathway. Such events culminate in the robust production of type I interferons, thus linking defective histone pre-mRNA processing with autoinflammatory responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these findings underscore the pivotal role of RNU7-1 in maintaining chromatin integrity by directing the precise processing of replication-dependent histone transcripts. When RNU7-1 function is compromised, the resultant histone imbalances precipitate chromatin decompaction that is immunogenic, ultimately invoking a cGAS-mediated interferon response that contributes to the pathogenesis of type I interferonopathies, such as Aicardi‐Goutiérès syndrome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Carolina Uggenti, Alice Lepelley, Marine Depp, et al. "}, {"type": "b", "children": [{"type": "t", "text": "cGAS-mediated induction of type I interferon due to inborn errors of histone pre-mRNA processing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41588-020-00737-3"}], "href": "https://doi.org/10.1038/s41588-020-00737-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33230297"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33230297"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Leslie Naesens, Josephine Nemegeer, Filip Roelens, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in RNU7-1 Weaken Secondary RNA Structure, Induce MCP-1 and CXCL10 in CSF, and Result in Aicardi-Goutières Syndrome with Severe End-Organ Involvement."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Immunol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10875-022-01209-5"}], "href": "https://doi.org/10.1007/s10875-022-01209-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35320431"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35320431"}]}]}]}