{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nU6 small nuclear RNA (RNU6‑1) plays dual roles in biomedical research. In liquid biopsy studies, it is commonly employed as a stable endogenous control for quantitative PCR analysis of microRNAs. Its robust and invariant expression in serum and liver samples has been benchmarked against candidate reference microRNAs, ensuring accurate miRNA quantitation for disease diagnosis and biomarker discovery."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n \nBeyond its utility as a normalization control, RNU6‑1 is a core component of the spliceosome. Structural and biophysical investigations demonstrate that U6 snRNA, together with U2 snRNA, forms dynamic complexes that adopt multiple conformations, a flexibility that is critical for pre‑mRNA splicing. Moreover, emerging evidence has revealed that U6 snRNA undergoes specific chemical modifications—most notably N2‑methylguanosine at position 72—installed by dedicated methyltransferases such as THUMPD2. These modifications, along with interactions with additional methyltransferases like TRMT11 and THUMPD3, fine‑tune its catalytic function during splicing."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n \nRecent studies underscore the versatility of U6 snRNA in regulating splice site choice. Its ability to form non‑canonical base pairing interactions, including extended Watson–Crick pairings with downstream regulatory sequences, facilitates the selection of tandem donor splice sites and modulates alternative splicing decisions. This additional layer of regulation further highlights the central role of RNU6‑1 in achieving spliceosomal precision."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Guixi Zheng, Haiyan Wang, Xin Zhang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "N 2-methylguanosine modifications on human tRNAs and snRNA U6 are important for cell proliferation, protein translation and pre-mRNA splicing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkad487"}], "href": "https://doi.org/10.1093/nar/gkad487"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37283053"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37283053"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Wen-Qing Yang, Jian-Yang Ge, Xiaofeng Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "THUMPD2 catalyzes the N2-methylation of U6 snRNA of the spliceosome catalytic center and regulates pre-mRNA splicing and retinal degeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkad1243"}], "href": "https://doi.org/10.1093/nar/gkad1243"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38165050"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38165050"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Michal Kramárek, Přemysl Souček, Kamila Réblová, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Splicing analysis of STAT3 tandem donor suggests non-canonical binding registers for U1 and U6 snRNAs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkae147"}], "href": "https://doi.org/10.1093/nar/gkae147"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38426935"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38426935"}]}]}]}