{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRBM45, originally identified as a neural RNA‐binding protein (also termed Drb1) with four conserved RNA recognition motifs, plays key roles in neural development and is increasingly implicated in neurodegenerative diseases. Early studies demonstrated its neuron‐specific expression and developmental regulation, while subsequent investigations revealed altered RBM45 levels in the cerebrospinal fluid of amyotrophic lateral sclerosis (ALS) patients along with its accumulation in cytoplasmic inclusions in ALS, frontotemporal lobar degeneration (FTLD), and Alzheimer’s disease. Furthermore, RBM45 forms homo‐oligomers via a conserved homo‐oligomer assembly (HOA) domain and interacts with other ALS-linked RNA binding proteins—such as TDP-43 and FUS—to influence mRNA splicing and stress granule dynamics, with loss of proper nuclear localization being associated with a loss-of-function mechanism in familial FTD-ALS."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its roles in RNA metabolism, RBM45 contributes to the maintenance of genomic stability. It is recruited to laser-induced DNA damage sites in a poly (ADP-ribose) (PAR)- and FUS-dependent manner, where it modulates double-strand break repair by competing with histone deacetylase 1 for binding to FUS, thus influencing the DNA damage response. Complementarily, RBM45 functions as an essential host factor in human parvovirus B19 infection by binding with high affinity to intronic splicing enhancer elements critical for the maturation of viral pre-mRNA encoding an 11-kDa nonstructural protein, illustrating its versatile involvement in RNA splicing regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nHigh-resolution structural and computational studies have further clarified the molecular underpinnings of RBM45 function. The crystal structure of its tandem RNA recognition motifs in complex with single-stranded nucleic acids has demonstrated specific recognition of a GAC sequence, with key aromatic and arginine residues—along with the interdomain linker—being critical for binding. Molecular dynamics simulations corroborate these findings by showing that mutations in these residues disrupt both van der Waals and electrostatic interactions, thereby impairing nucleic acid binding. Beyond neuronal contexts, RBM45 also modulates lipid metabolism reprogramming in hepatocellular carcinoma by directly regulating enzymes implicated in both de novo fatty acid synthesis and fatty acid β-oxidation, suggesting novel therapeutic avenues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hiroshi Tamada, Eiji Sakashita, Kuniko Shimazaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "cDNA cloning and characterization of Drb1, a new member of RRM-type neural RNA-binding protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0006-291x(02)02132-0"}], "href": "https://doi.org/10.1016/s0006-291x(02"}, {"type": "t", "text": "02132-0) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12220514"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12220514"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Mahlon Collins, David Riascos, Tina Kovalik, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The RNA-binding motif 45 (RBM45) protein accumulates in inclusion bodies in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Neuropathol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00401-012-1045-x"}], "href": "https://doi.org/10.1007/s00401-012-1045-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22993125"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22993125"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Nadine Bakkar, Arianna Kousari, Tina Kovalik, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "RBM45 homo-oligomerization mediates association with ALS-linked proteins and stress granules."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep14262"}], "href": "https://doi.org/10.1038/srep14262"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26391765"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26391765"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yang Li, Mahlon Collins, Jiyan An, et al. 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