{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nC14orf166, also known as RTRAF or hCLE, is a multifunctional protein that plays a central role in RNA metabolism. It modulates nuclear RNA processing by interacting with RNA polymerase II, thereby influencing transcription initiation, elongation, and processing. In addition, C14orf166 is involved in nucleo‐cytoplasmic RNA transport—it shuttles between the nucleus and cytoplasm as part of RNA granule complexes containing factors such as DDX1, HSPC117, and FAM98 proteins. These activities underline its importance in regulating gene expression at multiple levels."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of viral infections, C14orf166 has been shown to interact with viral proteins, thereby influencing the virus life cycle. The protein binds to the hepatitis C virus core protein—potentially impacting mRNA metabolism, gene regulation, and even microtubule organization—and to the influenza virus polymerase complex where it stimulates viral RNA transcription and replication. Notably, during influenza infection, C14orf166 is maintained or even increased despite host transcriptional shut-off, and it is found in association with viral ribonucleoproteins both in the nucleus and cytoplasm, even becoming incorporated within mature virions, suggesting a multifaceted role in facilitating efficient viral propagation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAberrant overexpression of C14orf166 has been documented in several human cancers, where it correlates with aggressive clinical behavior and poor patient outcomes. In pancreatic cancer, for example, higher expression levels are associated with lymph node metastasis, suggesting a role in tumor dissemination. Similarly, in cervical and nasopharyngeal carcinomas high C14orf166 expression is linked to advanced disease stage, larger tumor size, and reduced overall survival. Increased expression is also noted in bladder and breast cancers, and it appears that through its actions on transcription and RNA processing—as well as its interplay with other molecular partners (for instance, within complexes that modulate oncogenic proteins like PRMT1)—C14orf166 contributes to tumor progression and metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alicia Pérez-González, Alejandra Pazo, Rosana Navajas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "hCLE/C14orf166 associates with DDX1-HSPC117-FAM98B in a novel transcription-dependent shuttling RNA-transporting complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0090957"}], "href": "https://doi.org/10.1371/journal.pone.0090957"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24608264"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24608264"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Elif Çağlayan, Kadir Turan "}, {"type": "b", "children": [{"type": "t", "text": "An in silico prediction of interaction models of influenza A virus PA and human C14orf166 protein from yeast-two-hybrid screening data."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proteins (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/prot.26534"}], "href": "https://doi.org/10.1002/prot.26534"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37265372"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37265372"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jun-Wei Lee, Pao-Chi Liao, Kung-Chia Young, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of hnRNPH1, NF45, and C14orf166 as novel host interacting partners of the mature hepatitis C virus core protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Proteome Res (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/pr200338d"}], "href": "https://doi.org/10.1021/pr200338d"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21823664"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21823664"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ariel Rodriguez-Frandsen, Susana de Lucas, Alicia Pérez-González, et al. 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