{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DHX35 is a DEAH‐box RNA helicase that has emerged as a multifunctional factor primarily involved in the regulation of pre–mRNA splicing and may also contribute to disease susceptibility. Initial functional studies in spliceosome complexes indicate that DHX35 associates with a group of splicing factors—in particular, it displays coordinated behavior with the G–patch protein GPATCH1—that appears to promote splicing fidelity by suppressing the use of cryptic splice sites. In support of this role, analyses of spliceosomal complexes reveal that DHX35 is present during active spliceosome assembly but is subsequently lost during transitions into post–catalytic states, suggesting that its timely removal is important for correct exon ligation and mRNA release."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In parallel, genetic epidemiology studies have implicated DHX35 in human disease. Genome–wide association approaches have identified single–nucleotide polymorphisms within or near DHX35 (for example, rs6028466 and rs7267944) as components of polygenic “teloscores” associated with risks for pancreatic ductal adenocarcinoma and pancreatic neuroendocrine neoplasms"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", and as novel susceptibility variants for differentiated thyroid cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Epigenomic investigations in breast carcinogenesis have also recognized DHX35 among a panel of genes whose methylation changes may mediate the antagonistic effects of protective agents against chemically induced tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, inclusion of DHX35 in a biomarker gene panel for postmenopausal osteoporosis suggests potential roles in cellular processes affecting bone homeostasis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", while comparisons of helicase families in parasitic organisms highlight characteristic differences in DHX35 that may inform future therapeutic targeting."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, transcriptomic analyses have detected fusion events involving DHX35 (for instance, a DHX35–BPIFA2 fusion transcript) in colorectal cancer samples, further underscoring its potential involvement in oncogenic processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Collectively, these studies support a multifaceted role for DHX35 in maintaining splicing accuracy while also implicating it as a genetic and epigenetic marker in diverse human diseases. Further mechanistic studies will be required to fully delineate its contributions to RNA processing and disease pathogenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jade Sales-Lee, Daniela S Perry, Bradley A Bowser, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Coupling of spliceosome complexity to intron diversity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cub.2021.09.004"}], "href": "https://doi.org/10.1016/j.cub.2021.09.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34555349"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34555349"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Françoise Bonnet, Mickael Guedj, Natalie Jones, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An array CGH based genomic instability index (G2I) is predictive of clinical outcome in breast cancer and reveals a subset of tumors without lymph node involvement but with poor prognosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Med Genomics (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1755-8794-5-54"}], "href": "https://doi.org/10.1186/1755-8794-5-54"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23186559"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23186559"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Daniele Campa, Martina Matarazzi, William Greenhalf, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.31928"}], "href": "https://doi.org/10.1002/ijc.31928"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30325019"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30325019"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Manuel Gentiluomo, Gabriele Capurso, Luca Morelli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetically Determined Telomere Length Is Associated with Pancreatic Neuroendocrine Neoplasms Onset."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuroendocrinology (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000524659"}], "href": "https://doi.org/10.1159/000524659"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35472852"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35472852"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Gisella Figlioli, Aleksandra Köhler, Bowang Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel genome-wide association study-based candidate loci for differentiated thyroid cancer risk."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2014-1734"}], "href": "https://doi.org/10.1210/jc.2014-1734"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25029422"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25029422"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Zhuo-Zhi Liang, Yi-Xin Zhang, Rui-Mei Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of epigenetic modifications mediating the antagonistic effect of selenium against cadmium-induced breast carcinogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Environ Sci Pollut Res Int (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11356-021-17355-z"}], "href": "https://doi.org/10.1007/s11356-021-17355-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34773240"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34773240"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Chenggang Yang, Jing Ren, Bangling Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of gene biomarkers in patients with postmenopausal osteoporosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2018.9752"}], "href": "https://doi.org/10.3892/mmr.2018.9752"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30569177"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30569177"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Renu Tuteja, Abulaish Ansari, Anita, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome wide computational analysis of Brugia malayi helicases: a comparison with human host."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2012.02.036"}], "href": "https://doi.org/10.1016/j.gene.2012.02.036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22398250"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22398250"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Andreas M Hoff, Bjarne Johannessen, Sharmini Alagaratnam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel RNA variants in colorectal cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.5500"}], "href": "https://doi.org/10.18632/oncotarget.5500"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26474385"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26474385"}]}]}]}