{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Recent studies have expanded the functional repertoire of BUD13, establishing it as a multifunctional regulator that links RNA processing with metabolic homeostasis and disease susceptibility. At the molecular level, BUD13 functions as an integral component of the spliceosomal retention and splicing (RES) complex. It binds to pre‐mRNA to facilitate accurate spliceosome assembly—stabilizing weak U2/branch‐site interactions—and thereby modulates splice site selection. In yeast and mammalian systems, this activity is critical for preventing aberrant intron retention in key transcripts such as IRF7 and MED20, with consequent effects on immune responses and transcription regulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " BUD13 has also been shown to interact directly with specific microRNA precursors to influence their processing and stability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In parallel, genetic association studies have robustly implicated variants in the BUD13‐containing gene cluster—often analyzed together with neighboring loci such as ZNF259 and APOA5—in the regulation of serum lipid levels and metabolic syndrome components. Multiple genome‐wide analyses have demonstrated that common single‐nucleotide polymorphisms within this region are associated with altered triglyceride levels, dyslipidemia, impaired statin response, and type 2 diabetes risk."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "12"}]}, {"type": "t", "text": " In addition, novel BUD13 loci have been linked to variations in individual metabolic complements such as waist circumference and HDL‐cholesterol."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its roles in RNA splicing and metabolic regulation, BUD13 has emerged as a player in cancer. For instance, in certain malignancies the upregulation of BUD13 and its recruitment by long noncoding RNAs has been shown to stabilize mRNAs—such as that of fibronectin 1—thereby promoting cell proliferation, migration, and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the dual functions of BUD13 as an RNA‐binding protein critical for spliceosome fidelity and as a genetic determinant influencing lipid levels and metabolic traits. This multifunctionality positions BUD13 at the interface of gene expression regulation and metabolic as well as oncogenic processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Stéphane Hausmann, Sushuang Zheng, Michael Costanzo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic and biochemical analysis of yeast and human cap trimethylguanosine synthase: functional overlap of 2,2,7-trimethylguanosine caps, small nuclear ribonucleoprotein components, pre-mRNA splicing factors, and RNA decay pathways."}]}, {"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.M806127200"}], "href": "https://doi.org/10.1074/jbc.M806127200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18775984"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18775984"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yang Zhou, Marcus J O Johansson "}, {"type": "b", "children": [{"type": "t", "text": "The pre-mRNA retention and splicing complex controls expression of the Mediator subunit Med20."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15476286.2017.1294310"}], "href": "https://doi.org/10.1080/15476286.2017.1294310"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28277935"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28277935"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Luke Frankiw, Devdoot Majumdar, Christian Burns, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BUD13 Promotes a Type I Interferon Response by Countering Intron Retention in Irf7."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2018.11.038"}], "href": "https://doi.org/10.1016/j.molcel.2018.11.038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30639243"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30639243"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Julia K Nussbacher, Gene W Yeo "}, {"type": "b", "children": [{"type": "t", "text": "Systematic Discovery of RNA Binding Proteins that Regulate MicroRNA Levels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2018.02.012"}], "href": "https://doi.org/10.1016/j.molcel.2018.02.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29547715"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29547715"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Timothy R Braun, Latonya F Been, Akhil Singhal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A replication study of GWAS-derived lipid genes in Asian Indians: the chromosomal region 11q23.3 harbors loci contributing to triglycerides."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0037056"}], "href": "https://doi.org/10.1371/journal.pone.0037056"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22623978"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22623978"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yimin Zhu, Dandan Zhang, Dan Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Susceptibility loci for metabolic syndrome and metabolic components identified in Han Chinese: a multi-stage genome-wide association study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.13042"}], "href": "https://doi.org/10.1111/jcmm.13042"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28371326"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28371326"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Tina Shah, Delilah Zabaneh, Tom Gaunt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gene-centric analysis identifies variants associated with interleukin-6 levels and shared pathways with other inflammation markers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Cardiovasc Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCGENETICS.112.964254"}], "href": "https://doi.org/10.1161/CIRCGENETICS.112.964254"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23505291"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23505291"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Fanglin Guan, Yu Niu, Tianxiao Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two-stage association study to identify the genetic susceptibility of a novel common variant of rs2075290 in ZPR1 to type 2 diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep29586"}], "href": "https://doi.org/10.1038/srep29586"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27411854"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27411854"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Lynn Htet Htet Aung, Rui-Xing Yin, Dong-Feng Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of the variants in the BUD13-ZNF259 genes and the risk of hyperlipidaemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.12291"}], "href": "https://doi.org/10.1111/jcmm.12291"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24780069"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24780069"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Qianxi Fu, Xiaojun Tang, Juan Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effects of Polymorphisms in APOA4-APOA5-ZNF259-BUD13 Gene Cluster on Plasma Levels of Triglycerides and Risk of Coronary Heart Disease in a Chinese Han Population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0138652"}], "href": "https://doi.org/10.1371/journal.pone.0138652"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26397108"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26397108"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Sarah E OʼBrien, Steven J Schrodi, Zhan Ye, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential Lipid Response to Statins Is Associated With Variants in the BUD13-APOA5 Gene Region."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cardiovasc Pharmacol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/FJC.0000000000000261"}], "href": "https://doi.org/10.1097/FJC.0000000000000261"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25900265"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25900265"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Han-Kyul Kim, Muhammad Ayaz Anwar, Sangdun Choi "}, {"type": "b", "children": [{"type": "t", "text": "Association of BUD13-ZNF259-APOA5-APOA1-SIK3 cluster polymorphism in 11q23.3 and structure of APOA5 with increased plasma triglyceride levels in a Korean population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-019-44699-x"}], "href": "https://doi.org/10.1038/s41598-019-44699-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31165758"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31165758"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Lili Zhang, Yueyue You, Yanhua Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of BUD13 polymorphisms with metabolic syndrome in Chinese population: a case-control study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lipids Health Dis (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12944-017-0520-8"}], "href": "https://doi.org/10.1186/s12944-017-0520-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28659142"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28659142"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Yanping Song, Feng Gao, Yi Peng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA DBH-AS1 promotes cancer progression in diffuse large B-cell lymphoma by targeting FN1 via RNA-binding protein BUD13."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Biol Int (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cbin.11327"}], "href": "https://doi.org/10.1002/cbin.11327"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32091157"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32091157"}]}]}]}