{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPABPN1 plays a central role in nuclear RNA metabolism by enhancing mRNA polyadenylation and directing pre‐mRNA processing. It increases the processivity of poly(A) polymerase to generate full‐length poly(A) tails and exerts control over alternative cleavage and polyadenylation events—promoting distal polyadenylation site usage, regulating 3′ untranslated region lengths, and thereby influencing RNA stability and translation. In addition, PABPN1 facilitates efficient splicing of terminal introns in the context of 3′‐end formation, drives polyadenylation‐dependent maturation of telomerase RNA, and stimulates hyperadenylation that earmarks aberrant nuclear RNAs (including long noncoding transcripts) for exosome‐mediated decay."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its core role in RNA processing, PABPN1 contributes to the fine‐tuning of gene expression by modulating mRNA translation and engaging in nuclear RNA surveillance. For example, a circular RNA originating from its own pre‐mRNA (CircPABPN1) can sequester the RNA‐binding protein HuR, thereby dampening HuR’s stimulatory effect on PABPN1 mRNA translation. Moreover, PABPN1 is functionally integrated into the poly(A) tail exosome targeting (PAXT) network, linking nuclear polyadenylated transcripts to their degradation machinery. Its activity is modulated by arginine methylation—a modification that reduces affinity for the nuclear import receptor transportin while favoring RNA binding—and it becomes phosphorylated in an ATM‐dependent manner upon DNA damage to promote efficient double‐strand break repair. In addition, wild‐type PABPN1 can enhance the translation of anti‐apoptotic factors, underscoring its role in cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn disease contexts—most notably oculopharyngeal muscular dystrophy (OPMD)—mutations in PABPN1 (typically polyalanine expansions) perturb its normal functions. Such mutant forms display aberrant oligomerization and fibril formation that foster the accumulation of insoluble nuclear aggregates. These inclusions sequester polyadenylated RNAs and essential regulatory proteins, disrupt proper RNA processing, and trigger apoptotic signaling. Altered self‐aggregation properties, misregulation of its own expression via feedback mechanisms, and consequent defects in mRNA turnover and stress responses contribute to muscle degeneration and other cellular dysfunctions observed in OPMD."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "35"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mathias Jenal, Ran Elkon, Fabricio Loayza-Puch, et al. 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