{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:07:35Z","timestamp":1790809655287,"version":"4.1.0"},"reference-count":104,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T00:00:00Z","timestamp":1689206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Texas Medical Branch","award":["P01 AI150585"],"award-info":[{"award-number":["P01 AI150585"]}]},{"DOI":"10.13039\/100000060","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 AI150585"],"award-info":[{"award-number":["P01 AI150585"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Virginia School of Medicine","award":["P01 AI150585"],"award-info":[{"award-number":["P01 AI150585"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Over the last decade, our understanding of spliceosome structure and function has significantly improved, refining the study of the impact of dysregulated splicing on human disease. As a result, targeted splicing therapeutics have been developed, treating various diseases including spinal muscular atrophy and Duchenne muscular dystrophy. These advancements are very promising and emphasize the critical role of proper splicing in maintaining human health. Herein, we provide an overview of the current information on the composition and assembly of early splicing complexes\u2014commitment complex and pre-spliceosome\u2014and their association with human disease.<\/jats:p>","DOI":"10.3390\/ijms241411412","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T00:28:06Z","timestamp":1689294486000},"page":"11412","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Early Splicing Complexes and Human Disease"],"prefix":"10.3390","volume":"24","author":[{"given":"Chloe K.","family":"Nagasawa","sequence":"first","affiliation":[{"name":"Human Pathophysiology and Translational Medicine Program, Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX 77555-5302, USA"},{"name":"Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555-5302, USA"},{"name":"Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, VA 22903-2628, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8538-1997","authenticated-orcid":false,"given":"Mariano A.","family":"Garcia-Blanco","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555-5302, USA"},{"name":"Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, VA 22903-2628, USA"},{"name":"Institute of Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555-5302, USA"},{"name":"Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555-5302, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/S0092-8674(00)80479-1","article-title":"Classification of Introns: U2-Type or U12-Type","volume":"91","author":"Sharp","year":"1997","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5495","DOI":"10.1073\/pnas.76.11.5495","article-title":"Antibodies to Small Nuclear RNAs Complexed with Proteins Are Produced by Patients with Systemic Lupus Erythematosus","volume":"76","author":"Lerner","year":"1979","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1038\/283220a0","article-title":"Are SnRNPs Involved in Splicing?","volume":"283","author":"Lerner","year":"1980","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"a032417","DOI":"10.1101\/cshperspect.a032417","article-title":"Structural Insights into Nuclear Pre-MRNA Splicing in Higher Eukaryotes","volume":"11","author":"Kastner","year":"2019","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1002\/wrna.1140","article-title":"Exon and Intron Definition in Pre-MRNA Splicing","volume":"4","author":"Baralle","year":"2013","journal-title":"WIREs RNA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/35057062","article-title":"Initial Sequencing and Analysis of the Human Genome","volume":"409","author":"Lander","year":"2001","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"182","DOI":"10.4161\/nucl.2.3.15876","article-title":"Where Splicing Joins Chromatin","volume":"2","year":"2011","journal-title":"Nucleus"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"a003707","DOI":"10.1101\/cshperspect.a003707","article-title":"Spliceosome Structure and Function","volume":"3","author":"Will","year":"2011","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1002\/wrna.1158","article-title":"Targeting RNA Splicing for Disease Therapy","volume":"4","author":"Havens","year":"2013","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1146\/annurev-biochem-091719-064225","article-title":"RNA Splicing by the Spliceosome","volume":"89","author":"Wilkinson","year":"2020","journal-title":"Annu. Rev. Biochem."},{"key":"ref_11","first-page":"3755","article-title":"Early Commitment of Yeast Pre-MRNA to the Spliceosome Pathway","volume":"8","author":"Legrain","year":"1988","journal-title":"Mol. Cell. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1101\/gad.7.6.1008","article-title":"A Functional Association between the 5\u2032 and 3\u2032 Splice Site Is Established in the Earliest Prespliceosome Complex (E) in Mammals","volume":"7","author":"Michaud","year":"1993","journal-title":"Genes Dev."},{"key":"ref_13","first-page":"4279","article-title":"The Spliceosome Assembly Pathway in Mammalian Extracts","volume":"12","author":"Jamison","year":"1992","journal-title":"Mol. Cell. Biol."},{"key":"ref_14","first-page":"84","article-title":"Exon Definition May Facilitate Splice Site Selection in RNAs with Multiple Exons","volume":"10","author":"Robberson","year":"1990","journal-title":"Mol. Cell. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/0092-8674(83)90432-4","article-title":"The U1 Small Nuclear RNA-Protein Complex Selectively Binds a 5\u2032 Splice Site in Vitro","volume":"33","author":"Mount","year":"1983","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1101\/gad.12.6.858","article-title":"A Cooperative Interaction between U2AF65 and MBBP\/SF1 Facilitates Branchpoint Region Recognition","volume":"12","author":"Berglund","year":"1998","journal-title":"Genes Dev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/0092-8674(85)90064-9","article-title":"Intron Sequences Involved in Lariat Formation during Pre-MRNA Splicing","volume":"41","author":"Reed","year":"1985","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0092-8674(00)80221-4","article-title":"Cross-Intron Bridging Interactions in the Yeast Commitment Complex Are Conserved in Mammals","volume":"89","author":"Abovich","year":"1997","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1101\/gad.5.12b.2534","article-title":"An ATP-Independent Complex Commits Pre-MRNA to the Mammalian Spliceosome Assembly Pathway","volume":"5","author":"Michaud","year":"1991","journal-title":"Genes Dev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e04986","DOI":"10.7554\/eLife.04986","article-title":"Crystal Structure of Human U1 SnRNP, a Small Nuclear Ribonucleoprotein Particle, Reveals the Mechanism of 5\u2032 Splice Site Recognition","volume":"4","author":"Kondo","year":"2015","journal-title":"eLife"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4113","DOI":"10.1002\/j.1460-2075.1994.tb06729.x","article-title":"The Association of the U1-Specific 70K and C Proteins with U1 SnRNPs Is Mediated in Part by Common U SnRNP Proteins","volume":"13","author":"Nelissen","year":"1994","journal-title":"EMBO J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1080\/15476286.2022.2100971","article-title":"Principles and Correction of 5\u2032-Splice Site Selection","volume":"19","author":"Malard","year":"2022","journal-title":"RNA Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e27592","DOI":"10.7554\/eLife.27592","article-title":"Dynamics and Consequences of Spliceosome E Complex Formation","volume":"6","author":"Larson","year":"2017","journal-title":"eLife"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3260","DOI":"10.1093\/nar\/23.16.3260","article-title":"U1 SnRNP-ASF\/SF2 Interaction and 5\u2032 Splice Site Recognition: Characterization of Required Elements","volume":"23","author":"Jamison","year":"1995","journal-title":"Nucleic Acids Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8233","DOI":"10.1073\/pnas.1017700108","article-title":"Interaction between the RNA Binding Domains of Ser-Arg Splicing Factor 1 and U1-70K SnRNP Protein Determines Early Spliceosome Assembly","volume":"108","author":"Cho","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1042\/bst0210605","article-title":"Model of the Interaction between the UI A Small Nuclear Ribonucleoprotein and UI Small Nuclear RNA Stem\/Loop II","volume":"21","author":"Evans","year":"1993","journal-title":"Biochem. Soc. Trans."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/372432a0","article-title":"Crystal Structure at 1.92 \u00c5 Resolution of the RNA-Binding Domain of the U1A Spliceosomal Protein Complexed with an RNA Hairpin","volume":"372","author":"Oubridge","year":"1994","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1101\/gad.248625.114","article-title":"Stem\u2013Loop 4 of U1 SnRNA Is Essential for Splicing and Interacts with the U2 SnRNP-Specific SF3A1 Protein during Spliceosome Assembly","volume":"28","author":"Sharma","year":"2014","journal-title":"Genes Dev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.1080\/15476286.2021.1932360","article-title":"Synergistic Roles for Human U1 SnRNA Stem-Loops in Pre-MRNA Splicing","volume":"18","author":"Martelly","year":"2021","journal-title":"RNA Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2604","DOI":"10.1016\/S0021-9258(18)32969-7","article-title":"Isolation of Small Nuclear Ribonucleoproteins Containing U1, U2, U4, U5, and U6 RNAs","volume":"258","author":"Hinterberger","year":"1983","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1002\/wrna.87","article-title":"Biogenesis of Spliceosomal Small Nuclear Ribonucleoproteins","volume":"2","author":"Fischer","year":"2011","journal-title":"WIREs RNA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4971","DOI":"10.1093\/nar\/13.13.4971","article-title":"Intron Splicing: A Conserved Internal Signal in Introns of Drosophila Pre-MRNAs","volume":"13","author":"Keller","year":"1985","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1093\/nar\/gkn073","article-title":"Human Branch Point Consensus Sequence Is YUnAy","volume":"36","author":"Gao","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1126\/science.1064719","article-title":"Structural Basis for Recognition of the Intron Branch Site RNA by Splicing Factor 1","volume":"294","author":"Liu","year":"2001","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1017\/S1355838298980499","article-title":"The KH Domain of the Branchpoint Sequence Binding Protein Determines Specificity for the Pre-MRNA Branchpoint Sequence","volume":"4","author":"Berglund","year":"1998","journal-title":"RNA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/S1097-2765(03)00115-1","article-title":"Structural Basis for the Molecular Recognition between Human Splicing Factors U2AF65 and SF1\/MBBP","volume":"11","author":"Selenko","year":"2003","journal-title":"Mol. Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.molcel.2006.05.025","article-title":"Structural Basis for Polypyrimidine Tract Recognition by the Essential Pre-MRNA Splicing Factor U2AF65","volume":"23","author":"Sickmier","year":"2006","journal-title":"Mol. Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1038\/nature10171","article-title":"Multi-Domain Conformational Selection Underlies Pre-MRNA Splicing Regulation by U2AF","volume":"475","author":"Mackereth","year":"2011","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"11222","DOI":"10.1016\/S0021-9258(18)82114-7","article-title":"A Mutational Analysis of the Polypyrimidine Tract of Introns. Effects of Sequence Differences in Pyrimidine Tracts on Splicing","volume":"268","author":"Roscigno","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1017\/S1355838200000376","article-title":"Differential Recognition of the Polypyrimidine-Tract by the General Splicing Factor U2AF65 and the Splicing Repressor Sex-Lethal","volume":"6","author":"Singh","year":"2000","journal-title":"RNA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e76927","DOI":"10.7554\/eLife.76927","article-title":"The RNA Helicase DDX39B Activates FOXP3 RNA Splicing to Control T Regulatory Cell Fate","volume":"12","author":"Hirano","year":"2023","journal-title":"eLife"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5299","DOI":"10.1093\/nar\/gkac287","article-title":"Pre-MRNA Splicing Factor U2AF2 Recognizes Distinct Conformations of Nucleotide Variants at the Center of the Pre-MRNA Splice Site Signal","volume":"50","author":"Glasser","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_43","first-page":"E7169","article-title":"Recognition of the 3\u2032 Splice Site RNA by the U2AF Heterodimer Involves a Dynamic Population Shift","volume":"113","author":"Kang","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3859","DOI":"10.1093\/nar\/gkt046","article-title":"U2AF65 Adapts to Diverse Pre-MRNA Splice Sites through Conformational Selection of Specific and Promiscuous RNA Recognition Motifs","volume":"41","author":"Jenkins","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1261\/rna.057950.116","article-title":"Unmasking the U2AF Homology Motif Family: A Bona Fide Protein\u2013Protein Interaction Motif in Disguise","volume":"22","author":"Loerch","year":"2016","journal-title":"RNA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1038\/45590","article-title":"Functional Recognition of the 3\u2032 Splice Site AG by the Splicing Factor U2AF35","volume":"402","author":"Wu","year":"1999","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1101\/gad.267104.115","article-title":"A Novel 3\u2032 Splice Site Recognition by the Two Zinc Fingers in the U2AF Small Subunit","volume":"29","author":"Yoshida","year":"2015","journal-title":"Genes Dev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.14348\/molcells.2017.2319","article-title":"SR Proteins: Binders, Regulators, and Connectors of RNA","volume":"40","author":"Jeong","year":"2017","journal-title":"Mol. Cells"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/0092-8674(93)90316-I","article-title":"Specific Interactions between Proteins Implicated in Splice Site Selection and Regulated Alternative Splicing","volume":"75","author":"Wu","year":"1993","journal-title":"Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/368119a0","article-title":"Protein-Protein Interactions and 5\u2032-Splice-Site Recognition in Mammalian MRNA Precursors","volume":"368","author":"Kohtz","year":"1994","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1101\/gad.11.14.1864","article-title":"U2AF65 Recruits a Novel Human DEAD Box Protein Required for the U2 SnRNP-Branchpoint Interaction","volume":"11","author":"Fleckner","year":"1997","journal-title":"Genes Dev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1101\/gad.851701","article-title":"Identification and Characterization of YUAP\/Sub2p, a Yeast Homolog of the Essential Human Pre-MRNA Splicing Factor HUAP56","volume":"15","author":"Zhang","year":"2001","journal-title":"Genes Dev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/s41586-021-03789-5","article-title":"Structural Insights into How Prp5 Proofreads the Pre-MRNA Branch Site","volume":"596","author":"Zhang","year":"2021","journal-title":"Nature"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.1091\/mbc.e09-10-0913","article-title":"The Closely Related RNA Helicases, UAP56 and URH49, Preferentially Form Distinct MRNA Export Machineries and Coordinately Regulate Mitotic Progression","volume":"21","author":"Yamazaki","year":"2010","journal-title":"MBoC"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.cell.2017.03.007","article-title":"Human Epistatic Interaction Controls IL7R Splicing and Increases Multiple Sclerosis Risk","volume":"169","author":"Briggs","year":"2017","journal-title":"Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1101\/gad.851601","article-title":"Deletion of MUD2, the Yeast Homolog of U2AF65, Can Bypass the Requirement for Sub2, an Essential Spliceosomal ATPase","volume":"15","author":"Kistler","year":"2001","journal-title":"Genes Dev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1002\/j.1460-2075.1991.tb07670.x","article-title":"Three Protein Factors (SF1, SF3 and U2AF) Function in Pre-Splicing Complex Formation in Addition to SnRNPs","volume":"10","author":"Utans","year":"1991","journal-title":"EMBO J"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/345270a0","article-title":"Human U2 SnRNA Can Function in Pre-MRNA Splicing in Yeast","volume":"345","author":"Shuster","year":"1990","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/0092-8674(86)90365-X","article-title":"U2 RNA from Yeast Is Unexpectedly Large and Contains Homology to Vertebrate U4, U5, and U6 Small Nuclear RNAs","volume":"47","author":"Ares","year":"1986","journal-title":"Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"8229","DOI":"10.1073\/pnas.90.17.8229","article-title":"Evidence That the 60-KDa Protein of 17S U2 Small Nuclear Ribonucleoprotein Is Immunologically and Functionally Related to the Yeast PRP9 Splicing Factor and Is Required for the Efficient Formation of Prespliceosomes","volume":"90","author":"Behrens","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1261\/rna.2030510","article-title":"Release of SF3 from the Intron Branchpoint Activates the First Step of Pre-MRNA Splicing","volume":"16","author":"Lardelli","year":"2010","journal-title":"RNA"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1126\/science.abm4245","article-title":"Structural Basis of Branch Site Recognition by the Human Spliceosome","volume":"375","author":"Tholen","year":"2022","journal-title":"Science"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4752","DOI":"10.1128\/MCB.18.8.4752","article-title":"A Potential Role for U2AF-SAP 155 Interactions in Recruiting U2 SnRNP to the Branch Site","volume":"18","author":"Gozani","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.1101\/gad.8.24.3008","article-title":"Dynamic Association of Proteins with the Pre-MRNA Branch Region","volume":"8","author":"MacMillan","year":"1994","journal-title":"Genes Dev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1080\/10409238.2019.1691497","article-title":"Structural and Functional Modularity of the U2 SnRNP in Pre-MRNA Splicing","volume":"54","author":"Hoskins","year":"2019","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"10842","DOI":"10.1093\/nar\/gkz765","article-title":"Dynamics of the DEAD-Box ATPase Prp5 RecA-like Domains Provide a Conformational Switch during Spliceosome Assembly","volume":"47","author":"Beier","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1126\/science.274.5287.605","article-title":"Tat-SF1: Cofactor for Stimulation of Transcriptional Elongation by HIV-1 Tat","volume":"274","author":"Zhou","year":"1996","journal-title":"Science"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Miller, H.B., Saunders, K.O., Tomaras, G.D., and Garcia-Blanco, M.A. (2009). Tat-SF1 Is Not Required for Tat Transactivation but Does Regulate the Relative Levels of Unspliced and Spliced HIV-1 RNAs. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005710"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2892","DOI":"10.1074\/jbc.RA118.006764","article-title":"The Pre-MRNA Splicing and Transcription Factor Tat-SF1 Is a Functional Partner of the Spliceosome SF3b1 Subunit via a U2AF Homology Motif Interface","volume":"294","author":"Loerch","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1111\/bpa.12133","article-title":"Aggregates of Small Nuclear Ribonucleic Acids (SnRNAs) in Alzheimer\u2019s Disease","volume":"24","author":"Hales","year":"2014","journal-title":"Brain Pathol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1038\/s41586-019-1651-z","article-title":"The U1 Spliceosomal RNA Is Recurrently Mutated in Multiple Cancers","volume":"574","author":"Shuai","year":"2019","journal-title":"Nature"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/s41586-019-1650-0","article-title":"Recurrent Noncoding U1 SnRNA Mutations Drive Cryptic Splicing in SHH Medulloblastoma","volume":"574","author":"Suzuki","year":"2019","journal-title":"Nature"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1038\/s43587-022-00290-0","article-title":"Alzheimer\u2019s Disease-Associated U1 SnRNP Splicing Dysfunction Causes Neuronal Hyperexcitability and Cognitive Impairment","volume":"2","author":"Chen","year":"2022","journal-title":"Nat. Aging"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"146203","DOI":"10.1016\/j.gene.2022.146203","article-title":"A Specific Gene-Splicing Alteration in the SNRNP70 Gene as a Hallmark of an ALS Subtype","volume":"818","author":"Nakaya","year":"2022","journal-title":"Gene"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.ccell.2015.04.008","article-title":"Mutant U2AF1 Expression Alters Hematopoiesis and Pre-MRNA Splicing In Vivo","volume":"27","author":"Shirai","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/leu.2014.303","article-title":"U2AF1 Mutations Alter Sequence Specificity of Pre-MRNA Binding and Splicing","volume":"29","author":"White","year":"2015","journal-title":"Leukemia"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.molcel.2016.04.011","article-title":"U2AF35(S34F) Promotes Transformation by Directing Aberrant ATG7 Pre-MRNA 3\u2032 End Formation","volume":"62","author":"Park","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1261\/rna.061432.117","article-title":"The Cancer-Associated U2AF35 470A>G (Q157R) Mutation Creates an in-Frame Alternative 5\u2032 Splice Site That Impacts Splicing Regulation in Q157R Patients","volume":"23","author":"Herdt","year":"2017","journal-title":"RNA"},{"key":"ref_79","first-page":"710","article-title":"Association between Pancreatic Cancer Risk and the Interaction of U2AF65 Gene Polymorphisms and Smoking","volume":"35","author":"Tian","year":"2014","journal-title":"Zhonghua Liuxingbingxue Zazhi"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"17148","DOI":"10.1074\/jbc.RA120.015339","article-title":"Representative Cancer-Associated U2AF2 Mutations Alter RNA Interactions and Splicing","volume":"295","author":"Maji","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"37750","DOI":"10.18632\/oncotarget.5647","article-title":"SF3A1 and Pancreatic Cancer: New Evidence for the Association of the Spliceosome and Cancer","volume":"6","author":"Tian","year":"2015","journal-title":"Oncotarget"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.molcel.2019.07.017","article-title":"Disease-Causing Mutations in SF3B1 Alter Splicing by Disrupting Interaction with SUGP1","volume":"76","author":"Zhang","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4680","DOI":"10.1038\/s41467-021-24852-9","article-title":"Haploinsufficiency of SF3B2 Causes Craniofacial Microsomia","volume":"12","author":"Timberlake","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.ajhg.2012.04.004","article-title":"Haploinsufficiency of SF3B4, a Component of the Pre-MRNA Spliceosomal Complex, Causes Nager Syndrome","volume":"90","author":"Bernier","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/0092-8674(82)90110-6","article-title":"Human U1 Loci: Genes for Human U1 RNA Have Dramatically Similar Genomic Environments","volume":"29","author":"Manser","year":"1982","journal-title":"Cell"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1016\/j.celrep.2019.09.066","article-title":"Postmortem Cortex Samples Identify Distinct Molecular Subtypes of ALS: Retrotransposon Activation, Oxidative Stress, and Activated Glia","volume":"29","author":"Tam","year":"2019","journal-title":"Cell Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/ng.1031","article-title":"Recurrent Mutations in the U2AF1 Splicing Factor in Myelodysplastic Syndromes","volume":"44","author":"Graubert","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/nature10496","article-title":"Frequent Pathway Mutations of Splicing Machinery in Myelodysplasia","volume":"478","author":"Yoshida","year":"2011","journal-title":"Nature"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.bbrc.2016.12.153","article-title":"The RNA Helicase DDX39B and Its Paralog DDX39A Regulate Androgen Receptor Splice Variant AR-V7 Generation","volume":"483","author":"Nakata","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1261\/rna.035410.112","article-title":"Cleavage and Polyadenylation Specificity Factor 1 (CPSF1) Regulates Alternative Splicing of Interleukin 7 Receptor (IL7R) Exon 6","volume":"19","author":"Evsyukova","year":"2013","journal-title":"RNA"},{"key":"ref_91","first-page":"E1761","article-title":"Soluble IL7R\u03b1 Potentiates IL-7 Bioactivity and Promotes Autoimmunity","volume":"110","author":"Highfill","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1038\/ng2103","article-title":"Interleukin 7 Receptor \u03b1 Chain ( IL7R ) Shows Allelic and Functional Association with Multiple Sclerosis","volume":"39","author":"Gregory","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"The International Multiple Sclerosis Genetics Consortium (2007). Risk Alleles for Multiple Sclerosis Identified by a Genomewide Study. N. Engl. J. Med., 357, 851\u2013862.","DOI":"10.1056\/NEJMoa073493"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1038\/ng2106","article-title":"Variation in Interleukin 7 Receptor \u03b1 Chain (IL7R) Influences Risk of Multiple Sclerosis","volume":"39","author":"Lundmark","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s10875-019-00684-7","article-title":"Regulatory T Cells: The Many Faces of Foxp3","volume":"39","author":"Georgiev","year":"2019","journal-title":"J. Clin. Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1182\/blood.2020004850","article-title":"SF3B1-Mutant MDS as a Distinct Disease Subtype: A Proposal from the International Working Group for the Prognosis of MDS","volume":"136","author":"Malcovati","year":"2020","journal-title":"Blood"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/leu.2013.336","article-title":"Landscape of Genetic Lesions in 944 Patients with Myelodysplastic Syndromes","volume":"28","author":"Haferlach","year":"2014","journal-title":"Leukemia"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1056\/NEJMoa1103283","article-title":"Somatic SF3B1 Mutation in Myelodysplasia with Ring Sideroblasts","volume":"365","author":"Papaemmanuil","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 Revision to the World Health Organization Classification of Myeloid Neoplasms and Acute Leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/ng.1032","article-title":"Exome Sequencing Identifies Recurrent Mutations of the Splicing Factor SF3B1 Gene in Chronic Lymphocytic Leukemia","volume":"44","author":"Quesada","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3649","DOI":"10.1038\/s41467-018-06063-x","article-title":"Aberrant Splicing and Defective MRNA Production Induced by Somatic Spliceosome Mutations in Myelodysplasia","volume":"9","author":"Shiozawa","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.celrep.2015.09.053","article-title":"Cancer-Associated SF3B1 Hotspot Mutations Induce Cryptic 3\u2032 Splice Site Selection through Use of a Different Branch Point","volume":"13","author":"Darman","year":"2015","journal-title":"Cell Rep."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.canlet.2020.10.010","article-title":"Splicing Factor SF3B1 Is Overexpressed and Implicated in the Aggressiveness and Survival of Hepatocellular Carcinoma","volume":"496","author":"Amado","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/ejhg.2016.176","article-title":"A Synonymous Splicing Mutation in the SF3B4 Gene Segregates in a Family with Highly Variable Nager Syndrome","volume":"25","author":"Cassina","year":"2017","journal-title":"Eur. J. Hum. Genet."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/14\/11412\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:12:13Z","timestamp":1760127133000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/14\/11412"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,13]]},"references-count":104,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["ijms241411412"],"URL":"https:\/\/doi.org\/10.3390\/ijms241411412","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,13]]}}}