{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nHuman mitochondrial RNase P is a protein‐only complex essential for the 5′‐end processing of precursor tRNAs, and at its catalytic core is the metallonuclease subunit PRORP (also known as MRPP3). Structural studies reveal that PRORP is recruited and activated through specific interactions with its partner proteins—TRMT10C and SDR5C1—which together coordinate precise substrate recognition and cleavage. Notably, genetic variation, including a missense mutation in the gene encoding PRORP, has been shown to influence posttranscriptional tRNA modifications and may impact mitochondrial energy production."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBiochemical and structural investigations have further demonstrated that human PRORP requires association with additional subunits to achieve a catalytically active state; in contrast to its homologs in plants and trypanosomes that function as single proteins, human PRORP is maintained in a tripartite complex. Mutations in PRORP have been linked to combined oxidative phosphorylation deficiency type 54 (COXPD54), manifesting as sensorineural hearing loss, primary ovarian insufficiency, developmental delay, and leukodystrophy. Functional assays employing recombinant proteins have confirmed that pathogenic variants in PRORP compromise mitochondrial pre‐tRNA cleavage, leading to accumulation of unprocessed transcripts and downstream deficiencies in mitochondrial protein synthesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in mitochondrial RNA processing, emerging evidence suggests that dysregulation of the PRORP gene (annotated as KIAA0391) can also contribute to oncogenic processes. In non‐small cell lung cancer, alterations in KIAA0391 expression have been implicated in the modulation of pyroptosis-related pathways, thereby promoting tumorigenesis through transcriptional repression of key effectors such as CASP1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alan Hodgkinson, Youssef Idaghdour, Elias Gbeha, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Bi-allelic variants in the mitochondrial RNase P subunit PRORP cause mitochondrial tRNA processing defects and pleiotropic multisystem presentations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2021.10.002"}], "href": "https://doi.org/10.1016/j.ajhg.2021.10.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34715011"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34715011"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Thomas B Smith, Alessandro Rea, Huw B Thomas, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Comprehensive functional interrogation of susceptibility loci in GWASs identified KIAA0391 as a novel oncogenic driver via regulating pyroptosis in NSCLC."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2024.216646"}], "href": "https://doi.org/10.1016/j.canlet.2024.216646"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38262497"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38262497"}]}]}]}