{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRNU12 encodes a small nuclear RNA that is an integral component of the minor (U12‐dependent) spliceosome—a specialized machinery responsible for the recognition and removal of U12‐type introns. Proper U12 spliceosome assembly is critical for accurate splicing, as exemplified by studies showing that disruption of its components (for example, mutations in the spliceosome factor ZRSR2) leads to selective retention of U12‐type introns and associated pathologies. This context underlines the importance of each constituent, including RNU12, in maintaining splicing fidelity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent investigations into the molecular consequences of specific RNU12 mutations have revealed that single‐nucleotide changes, such as the 84C>U variant, destabilize the U12 snRNA. This mutation precipitates accelerated decay and the accumulation of 3′-truncated decay intermediates, thereby reducing the steady-state levels of functional U12 snRNA. Such destabilization impairs the minor spliceosome’s capacity to correctly recognize and excise U12-type introns, contributing to aberrant splicing patterns observed in early-onset cerebellar ataxia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nComplementary findings from clinical genetic studies further support the indispensable role of RNU12 in development and tissue patterning. In patients with CDAGS syndrome, biallelic rare variants affecting conserved nucleotides within the precursor U12 snRNA compromise its secondary structure and critical binding sites, leading to alternative splicing events and mis-expression of downstream genes. These alterations correlate with clinical features such as craniosynostosis, clavicular hypoplasia, anal abnormalities, and cutaneous manifestations, emphasizing that precise RNU12 function is essential for normal minor intron splicing and developmental patterning."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Vikas Madan, Deepika Kanojia, Jia Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Aberrant splicing of U12-type introns is the hallmark of ZRSR2 mutant myelodysplastic syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms7042"}], "href": "https://doi.org/10.1038/ncomms7042"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25586593"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25586593"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Antto J Norppa, Mikko J Frilander "}, {"type": "b", "children": [{"type": "t", "text": "The integrity of the U12 snRNA 3' stem-loop is necessary for its overall stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkab048"}], "href": "https://doi.org/10.1093/nar/gkab048"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33577674"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33577674"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Chao Xing, Mohammed Kanchwala, Jonathan J Rios, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biallelic variants in RNU12 cause CDAGS syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.24239"}], "href": "https://doi.org/10.1002/humu.24239"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34085356"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34085356"}]}]}]}