{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nCanonical RNU1-1 encodes the U1 small nuclear RNA that is essential for accurate pre‐mRNA splicing. In addition to its classical role of recognizing 5′ splice sites and initiating spliceosome assembly, U1 snRNA safeguards nascent transcripts from premature cleavage and polyadenylation—a process termed “telescripting.” Two independent studies demonstrated that even moderate decreases in U1 levels result in a downstream shift of polyadenylation sites, mRNA shortening, and altered exon choices—mechanisms that help preserve transcriptome integrity and may dynamically regulate gene expression during cellular activation and differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its protective functions, the activity of U1 snRNA may be modulated by interactions with regulatory proteins. For example, association of the U1 snRNP with splicing regulators such as the polypyrimidine tract‐binding protein (PTB) alters splice site recognition and can repress alternative exon inclusion, thereby fine‐tuning spliceosomal activity. Moreover, engineered U1 snRNA variants that re‐establish proper 5′ splice site recognition have been successfully employed to correct splicing defects in genetic disorders such as aromatic l‐amino acid decarboxylase deficiency, underscoring the therapeutic potential of manipulating U1‐mediated splicing."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nComparative analyses further reveal that while the canonical RNU1-1 transcript is efficiently incorporated into functional snRNPs, a number of U1‐like variant transcripts exhibit cell type–specific expression patterns—for instance, being upregulated in stem cells—but generally show reduced capacity for interacting with core U1 snRNP proteins. This differential assembly suggests that variant U1 snRNAs could play nuanced roles in cell fate decisions by modulating the balance between canonical splicing and alternative processing events."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Michael G Berg, Larry N Singh, Ihab Younis, et al. 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