{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nU2AF1L4, a homolog of the small U2AF subunit, is a multifaceted splicing factor that contributes to the recognition of 3′ splice sites and regulation of alternative splicing. Studies have demonstrated that distinct isoforms of this protein display differential intracellular localization—one variant dynamically shuttles between the nucleus and cytoplasm due to a unique C‐terminal nuclear localization sequence, a feature that may govern its availability for splicing events. Such compartmentalization underscores the importance of U2AF1L4 in modulating spliceosome composition and function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAn evolutionarily conserved enhancer element located within the second intron of the U2AF1L4 gene has been characterized, revealing functional motifs that bind nuclear proteins and modulate transcription. This enhancer—by virtue of its conserved sequences across primate species—suggests a critical role in fine‐tuning U2AF1L4 gene expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt a broader genomic level, U2AF1L4 is positioned head‐to‐head with the PSENEN gene within a bidirectional promoter, enabling concerted divergent transcription that appears to be relevant for T-cell function. In T-lymphocytes, cytokines sharing a common gamma-chain (IL-2, IL-7, and IL-15) exert dose-dependent effects on U2AF1L4 mRNA levels—together with changes in regulators of alternative splicing such as Gfi1—thus impacting the splicing of key receptor isoforms like CD45 and influencing T-cell homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDetailed structural and functional analyses have further illuminated the importance of the zinc finger domains within U2AF1L4. These domains are not only essential for its splicing regulatory activity—through ensuring protein stability and mediating interactions with core splicing components—but also contribute to a cytoplasmic function whereby targeted localization to the 5′ untranslated region of mRNAs can enhance translation. This dual role in both nuclear pre-mRNA processing and cytoplasmic translation highlights the diverse regulatory capabilities of U2AF1L4."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Florian Heyd, Maria Carmo-Fonseca, Tarik Möröy "}, {"type": "b", "children": [{"type": "t", "text": "Differential isoform expression and interaction with the P32 regulatory protein controls the subcellular localization of the splicing factor U2AF26."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M801014200"}], "href": "https://doi.org/10.1074/jbc.M801014200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18460468"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18460468"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "D A Didych, N A Smirnov, E S Kotova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional dissection of an enhancer-like element located within the second intron of the human U2AF1L4 gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (Mosc) (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1134/S0006297911080116"}], "href": "https://doi.org/10.1134/S0006297911080116"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22022969"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22022969"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "D A Didych, M F Shamsutdinov, N A Smirnov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human PSENEN and U2AF1L4 genes are concertedly regulated by a genuine bidirectional promoter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2012.11.058"}], "href": "https://doi.org/10.1016/j.gene.2012.11.058"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23246698"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23246698"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "K A Yurova, N A Sokhonevich, O G Khaziakhmatova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Cytokine-mediated regulation of expression of Gfi1 and U2afll4 genes activated by T-cells with different differentiation status in vitro]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Khim (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18097/PBMC20166202180"}], "href": "https://doi.org/10.18097/PBMC20166202180"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27143377"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27143377"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Olga Herdt, Stefan Reich, Jan Medenbach, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The zinc finger domains in U2AF26 and U2AF35 have diverse functionalities including a role in controlling translation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15476286.2020.1732701"}], "href": "https://doi.org/10.1080/15476286.2020.1732701"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32116123"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32116123"}]}]}]}