{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nProtein arginine methyltransferase 5 (PRMT5) is a versatile epigenetic regulator that catalyzes the symmetric dimethylation of arginine residues on both histone and non‐histone proteins. By partnering with core components such as MEP50 and associating with chromatin‐remodeling complexes (e.g., hSWI/SNF), PRMT5 methylates the N‐terminal tails of histones H3 and H4—targeting residues such as H3R8, H4R3, and H3R2—to establish repressive chromatin marks. These modifications have been shown to repress key tumor suppressor genes, support maintenance of pluripotency in embryonic and germ cells, and facilitate proper assembly of small nuclear ribonucleoproteins during splicing and transcriptional control."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in chromatin architecture, PRMT5 is central to establishing repressive epigenetic landscapes that set the stage for subsequent DNA methylation and robust gene silencing. Aberrant PRMT5 activity has been implicated in a wide spectrum of human cancers—including lymphomas, leukemias, colorectal, breast, prostate, pancreatic, and glioblastoma—where it not only represses tumor suppressor loci (for example, ST7, NM23, and several cell‐cycle inhibitors) but also modulates the activity of key transcription factors such as NF‑κB and p53. Furthermore, metabolic perturbations like the accumulation of methylthioadenosine (MTA) in the context of MTAP deletion create a “hypomorphic” state for PRMT5 that confers selective vulnerability; these insights have spurred the development of small‐molecule inhibitors targeting the PRMT5 and MAT2A axes to arrest tumor growth."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "34"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its chromatin‐modifying activity, PRMT5 regulates RNA processing and signal transduction pathways that are pivotal for tumor cell survival and self‐renewal. By methylating splicing regulators and interacting with factors such as DDX5, RioK1, and nucleolin, PRMT5 influences alternative splicing decisions and the repair of DNA damage, thereby integrating epigenetic control with post‐transcriptional and signal transduction networks. These multifaceted roles enable PRMT5 to promote cell‐cycle progression; enhance oncogenic signaling via modification of kinases and transcription factors (e.g., modulating RAF turnover and NF‑κB p65 DNA‐binding affinity); and sustain cancer stem cell populations in aggressive tumors such as glioblastoma and breast cancer. Collectively, these discoveries not only illuminate the central role of PRMT5 in tumorigenesis and cellular homeostasis but also underscore its promise as a prognostic biomarker and a therapeutic target in diverse malignancies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "32"}, {"type": "fg_f", "ref": "34"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sharmistha Pal, Romy Yun, Antara Datta, et al. 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