{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTUT1 is a nucleotidyl transferase best known for its role in the maturation of U6 small nuclear RNA (snRNA), a catalytic component essential for pre‐mRNA splicing. By catalyzing the addition or repair of a short 3′ oligo‐uridylated tail on U6 snRNA, TUT1 generates the binding site for Lsm proteins that mediate U4/U6 di‑snRNP formation. Structural and biochemical analyses reveal that TUT1 specifically recognizes distinct sequence and structural elements within U6 snRNA, guiding an efficient oligouridylation process that continues until optimal base‑pairing is achieved."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its canonical function in snRNA processing, TUT1 appears to influence the cellular levels of microRNAs. Suppression of TUT1 has been observed to result in a global decrease in miRNA abundance—not as a direct consequence of altered 3′ nucleotide additions on specific miRNAs but rather via an indirect, post‑transcriptional mechanism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAlterations in TUT1 expression also have implications in human disease. In osteosarcoma, TUT1 is significantly downregulated compared with adjacent normal tissues. Restoration of TUT1 expression in osteosarcoma cells results in inhibited proliferation through the down‑regulation of key lipogenesis regulators via modulation of specific microRNAs, suggesting that TUT1 may function as a tumor suppressor in this cancer type."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, TUT1’s function and intracellular localization are subject to regulation by other proteins. For example, KLHL7, a component of a Cullin‑RING ubiquitin ligase complex, promotes the ubiquitination of TUT1, thereby reducing its localization within the nucleolus and potentially impacting nucleolar integrity and ribonucleoprotein assembly. Such alterations in TUT1 regulation may contribute to the pathogenesis of disorders like retinitis pigmentosa associated with pathogenic KLHL7 mutations."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Seisuke Yamashita, Yuko Takagi, Takashi Nagaike, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Migration of myeloid cells during inflammation is differentially regulated by the cell surface receptors Slamf1 and Slamf8."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0121968"}], "href": "https://doi.org/10.1371/journal.pone.0121968"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25799045"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25799045"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "De-Qiu Zhu, Yue-Fen Lou, Zhi-Gao He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nucleotidyl transferase TUT1 inhibits lipogenesis in osteosarcoma cells through regulation of microRNA-24 and microRNA-29a."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13277-014-2395-x"}], "href": "https://doi.org/10.1007/s13277-014-2395-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25142229"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25142229"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jaehyun Kim, Fuminori Tsuruta, Tomomi Okajima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KLHL7 promotes TUT1 ubiquitination associated with nucleolar integrity: Implications for retinitis pigmentosa."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2017.10.049"}], "href": "https://doi.org/10.1016/j.bbrc.2017.10.049"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29032201"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29032201"}]}]}]}