{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nARS2/SRRT is a multifunctional nuclear protein that plays a central role in RNA metabolism by orchestrating the fate of RNA polymerase II transcripts. Acting as an integral partner of the cap‐binding complex (CBC), ARS2 facilitates the biogenesis of specific microRNAs, supports proper 3′‐end processing of histone mRNAs and long noncoding RNAs (e.g. NEAT1), and helps ensure accurate transcription termination and RNA decay. ARS2 achieves these functions through defined interactions with diverse factors such as FLASH, NELF‐E, PHAX, 7SK, and NCBP3, thereby dynamically assembling mutually exclusive higher‐order complexes that direct transcript maturation or degradation."}, {"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": "\nIn several pathological settings, particularly in cancer, aberrant expression or function of ARS2 has been tightly linked to deregulated cell proliferation and tumorigenesis. Overexpression of ARS2 supports oncogenic programs in diverse malignancies—including glioblastoma, cholangiocarcinoma, hepatocellular carcinoma, and acute myeloid leukemia—by modulating the processing of key microRNAs (such as miR‐21, miR‐6798‐3p, and others), influencing cell cycle regulators (for instance, p53 and p21) and activating pro‐survival pathways such as MAPK/ERK or prostaglandin E₂ signaling. In addition, in glioblastoma the interplay between ARS2 and factors within the tumor microenvironment contributes to the regulation of stem cell maintenance and tumor‐associated cell polarization."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in RNA processing and oncogenesis, ARS2 is critical for normal development and physiological homeostasis. Its interaction with FLASH is indispensable for S phase progression, and loss of ARS2 results in early embryonic lethality, defective hematopoiesis, and increased apoptosis in developing tissues. Moreover, altered levels of ARS2 have been proposed as prognostic markers in childhood acute lymphoblastic leukemia and have been implicated in cellular responses to toxic insults such as arsenic‐induced nephrotoxicity—possibly through cross‐talk with antioxidant and ubiquitin‐dependent pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Joshua J Gruber, D Steven Zatechka, Leah R Sabin, et al. 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