{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have revealed that the protein product encoded by OR4F21—alternatively known as CBF‐A, AUF2, or Hnrnpab—serves as a multifunctional RNA‐binding regulator that modulates post‐transcriptional gene expression. Initial work demonstrated its ability to recognize AU‐rich elements (AREs) in transcripts such as those encoding cyclo-oxygenase-2 and tumor necrosis factor-alpha, thereby impacting mRNA stability. Moreover, distinct isoforms of this protein (p37 and p42) exhibit differential binding to regulatory elements in the 3′ UTR of target mRNAs, controlling the timing of mRNA translation in specialized cell types, including those integral to spermatogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional investigations have expanded the functional repertoire of OR4F21 to neural contexts. Its abundant expression in neural stem cell niches and developing neurons influences lineage specification, migration, and synapse assembly. In neural progenitors, both isoforms act cooperatively to regulate the transcription of genes critical for cell motility, such as Eps8, while in olfactory sensory neurons the protein directs axon targeting by binding to motifs in the 3′ UTRs of adhesion molecule transcripts. Consequently, loss of OR4F21 disrupts these processes, resulting in aberrant neuronal differentiation and increased vulnerability to excitotoxic stress."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in development, OR4F21 also participates in regulating inflammatory responses and host defense mechanisms. It has been implicated in modulating the transcription of pro-inflammatory genes by interacting with nitric oxide-induced post-translational modifications of transcriptional repressors, thereby facilitating processes such as mammary gland involution. In the context of viral infection, OR4F21 interferes with influenza A virus polymerase complex assembly by perturbing the NP-PB1 interaction, contributing to an effective antiviral response. These multifaceted roles underscore the significance of OR4F21 as a central regulator of diverse cellular processes, and they highlight how dysregulation may contribute to developmental abnormalities and disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAlthough some related studies have also explored factors involved in vascular injury responses, these findings further reinforce the critical importance of maintaining precise post-transcriptional control in adult tissues—a role in which OR4F21 is now being increasingly recognized."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jonathan L E Dean, Gareth Sully, Robin Wait, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The transacting factor CBF-A/Hnrnpab binds to the A2RE/RTS element of protamine 2 mRNA and contributes to its translational regulation during mouse spermatogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1003858"}], "href": "https://doi.org/10.1371/journal.pgen.1003858"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24146628"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24146628"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "John R Sinnamon, Catherine B Waddell, Sara Nik, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hnrpab regulates neural development and neuron cell survival after glutamate stimulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1261/rna.030742.111"}], "href": "https://doi.org/10.1261/rna.030742.111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22332140"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22332140"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Alexa A Lampasona, Kevin Czaplinski "}, {"type": "b", "children": [{"type": "t", "text": "Hnrnpab regulates neural cell motility through transcription of Eps8."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1261/rna.067413.118"}], "href": "https://doi.org/10.1261/rna.067413.118"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30314980"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30314980"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Nanaho Fukuda, Tomoyuki Fukuda, Piergiorgio Percipalle, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Axonal mRNA binding of hnRNP A/B is crucial for axon targeting and maturation of olfactory sensory neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2023.112398"}], "href": "https://doi.org/10.1016/j.celrep.2023.112398"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37083330"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37083330"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Chengjiang Gao, Hongtao Guo, Junping Wei, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Intronic CArG box regulates cysteine-rich protein 2 expression in the adult but not in developing vasculature."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/ATVBAHA.109.197251"}], "href": "https://doi.org/10.1161/ATVBAHA.109.197251"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20075421"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20075421"}]}]}]}