{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nXRN2 is a nuclear 5′‑3′ exoribonuclease that plays a central role in transcription termination by degrading nascent RNA transcripts. Studies have shown that following polyadenylation and co‑transcriptional cleavage (including self‑cleavage via CoTC elements), the free 5′ ends generated are efficiently degraded by XRN2, promoting RNA polymerase II release in support of the torpedo model of termination."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In addition, physical interactions between XRN2 and various 3′‑processing or decapping factors as well as with termination factors such as TTF2 facilitate its recruitment to the 3′‑end of genes, where its exonuclease activity—further enhanced by CDK9‐mediated phosphorylation—ensures robust termination and prevents readthrough transcription."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond classical transcription termination, XRN2 contributes to RNA quality control by co‑transcriptionally degrading aberrantly processed pre‑mRNAs and excised spacer fragments generated during ribosomal RNA maturation. XRN2 activity is also linked to proper recruitment of RNA‑binding factors like hnRNPK, while its localization and function in pre‑rRNA processing can be modulated by proteins such as CARF."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nXRN2 also safeguards genomic stability by resolving RNA/DNA hybrid structures (R‑loops) that form at transcription pause sites, thereby preventing replication stress and double‑strand break formation. In parallel, XRN2 regulates the stability of telomeric repeat‑containing RNAs (TERRA), impacting telomere homeostasis especially in cancer cells that rely on alternative lengthening of telomeres."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of viral infection and tumorigenesis, XRN2 exerts antiviral effects by degrading viral RNA—for example, limiting hepatitis C virus RNA accumulation—although its impact can be offset by protective factors such as miR‑122. Moreover, altered XRN2 expression and genetic variants that modulate its expression have been linked to lung cancer susceptibility and aggressive behavior in glioblastoma, with alternative splice forms possibly diversifying its functions in different tissues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nXRN2 further participates in post‑transcriptional regulation by interacting with RNA‑binding proteins such as Sam68, thereby influencing alternative polyadenylation events that result in 3′‑UTR shortening and enhanced translation of cell cycle regulators. 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