{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent evidence has revealed that pre‐mRNA processing factor 6 (PRPF6) plays multifaceted roles in RNA processing and transcriptional regulation. In one study, a protein originally isolated as ANT‐1, identical to the human homologue of yeast Prp6p, was shown to bind the androgen receptor (AR) activation function‐1 domain, thereby enhancing its ligand‐independent transactivation and establishing a spatial relationship between AR and splicing factor compartments."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn its canonical role, PRPF6 is an essential spliceosome component involved in the assembly and stability of the U4/U6.U5 tri‐snRNP complex. Phosphorylation studies revealed that PRPF6, along with other splicing factors, is a direct target of the PRP4 kinase, a modification critical for the formation of functional spliceosomal B complexes. Importantly, mutations in PRPF6, which lead to its aberrant nuclear localization (accumulation in Cajal bodies) and consequent intron retention, have been linked to dominantly inherited retinitis pigmentosa."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its fundamental role in splicing, PRPF6 has been implicated in cancer cell biology. One investigation demonstrated that inhibition of PRPF6 selectively suppressed growth in cancer cells by altering the splicing of a discrete set of genes involved in growth regulation; this preferential splicing is thought to drive cancer proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther studies have expanded the oncogenic portfolio of PRPF6 to include modulation of androgen receptor signaling. In hepatocellular carcinoma and prostate cancer models, PRPF6 interacts with both full‐length AR and its splice variants to enhance AR self-transcription and transactivation. This effect involves PRPF6 recruitment to AR target gene regulatory regions and association with chromatin‐modifying partners, thereby augmenting oncogenic AR signaling pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nLastly, PRPF6 also appears to foster more aggressive tumor phenotypes. In ovarian cancer, upregulation of PRPF6 is associated with enhanced metastasis and paclitaxel resistance. Mechanistically, PRPF6 modulates alternative splicing events (such as those affecting SNHG16 isoforms) that alter downstream transcription factor expression, linking aberrant splicing with tumor progression and chemoresistance. Moreover, interactions between PRPF6 and other spliceosomal components, including regulators of intranuclear tri-snRNP transfer, further underscore its broad impact on RNA maturation processes that can contribute to disease when perturbed."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yue Zhao, Kiminobu Goto, Masayuki Saitoh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation function-1 domain of androgen receptor contributes to the interaction between subnuclear splicing factor compartment and nuclear receptor compartment. Identification of the p102 U5 small nuclear ribonucleoprotein particle-binding protein as a coactivator for the receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M203811200"}], "href": "https://doi.org/10.1074/jbc.M203811200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12039962"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12039962"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Marc Schneider, He-Hsuan Hsiao, Cindy L Will, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human PRP4 kinase is required for stable tri-snRNP association during spliceosomal B complex formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb.1718"}], "href": "https://doi.org/10.1038/nsmb.1718"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20118938"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20118938"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Goranka Tanackovic, Adriana Ransijn, Carmen Ayuso, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A missense mutation in PRPF6 causes impairment of pre-mRNA splicing and autosomal-dominant retinitis pigmentosa."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2011.04.008"}], "href": "https://doi.org/10.1016/j.ajhg.2011.04.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21549338"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21549338"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Adam S Adler, Mark L McCleland, Sharon Yee, et al. 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