U2AF1

Summary

Gene Symbol: U2AF1
Description: U2 small nuclear RNA auxiliary factor 1
Alias: FP793, RNU2AF1, U2AF35, U2AFBP, splicing factor U2AF 35 kDa subunit, U2 small nuclear RNA auxillary factor 1, U2 small nuclear ribonucleoprotein auxillary factor, 35-KD subunit, U2 snRNP auxiliary factor small subunit, U2(RNU2) small nuclear RNA auxiliary factor binding protein, splicing factor U2AF 35kDa subunit
Species: human
Products:     U2AF1

Top Publications

  1. Zamore P, Green M. Biochemical characterization of U2 snRNP auxiliary factor: an essential pre-mRNA splicing factor with a novel intranuclear distribution. EMBO J. 1991;10:207-14 pubmed
    ..Our data, in conjunction with those in the accompanying paper [Carmo-Fonseca et al. (1991) EMBO J., 10, 195-206.], suggest that these centers represent novel aspects of nuclear organization. ..
  2. Zuo P, Maniatis T. The splicing factor U2AF35 mediates critical protein-protein interactions in constitutive and enhancer-dependent splicing. Genes Dev. 1996;10:1356-68 pubmed
    The splicing factor U2AF (U2 snRNP auxiliary factor) is a heterodimer with subunits of 65 and 35 kD (U2AF65 and U2AF35). U2AF65 binds specifically to 3' splice sites, but previous studies failed to demonstrate a function for U2AF35...
  3. Pacheco T, Moita L, Gomes A, Hacohen N, Carmo Fonseca M. RNA interference knockdown of hU2AF35 impairs cell cycle progression and modulates alternative splicing of Cdc25 transcripts. Mol Biol Cell. 2006;17:4187-99 pubmed
    U2AF is a heterodimeric splicing factor composed of a large (U2AF65) and a small (U2AF35) subunit. In humans, alternative splicing generates two U2AF35 variants, U2AF35a and U2AF35b...
  4. Tavanez J, Madl T, Kooshapur H, Sattler M, Valcarcel J. hnRNP A1 proofreads 3' splice site recognition by U2AF. Mol Cell. 2012;45:314-29 pubmed publisher
    ..Consistent with the functional relevance of this activity for splicing, proofreading assays reveal a role for hnRNP A1 in U2AF-mediated recruitment of U2 snRNP to the pre-mRNA. ..
  5. Zhang M, Zamore P, Carmo Fonseca M, Lamond A, Green M. Cloning and intracellular localization of the U2 small nuclear ribonucleoprotein auxiliary factor small subunit. Proc Natl Acad Sci U S A. 1992;89:8769-73 pubmed
    ..binds the pre-mRNA polypyrimidine tract and is required for in vitro splicing, and an associated 35-kDa protein (U2AF35). Here we report the isolation of a cDNA encoding U2AF35...
  6. Wu J, Maniatis T. Specific interactions between proteins implicated in splice site selection and regulated alternative splicing. Cell. 1993;75:1061-70 pubmed
    ..integral U1 small nuclear ribonucleoprotein (snRNP U1-70K) and with the 35 kd subunit of the splicing factor U2AF (U2AF35)...
  7. Tronchere H, Wang J, Fu X. A protein related to splicing factor U2AF35 that interacts with U2AF65 and SR proteins in splicing of pre-mRNA. Nature. 1997;388:397-400 pubmed
    Recognition of a functional 3' splice site in pre-mRNA splicing requires a heterodimer of the proteins U2AF65/U2AF35. U2AF65 binds to RNA at the polypyrimidine tract, whereas U2AF35 is thought to interact through its arginine/serine-rich (..
  8. Kielkopf C, Rodionova N, Green M, Burley S. A novel peptide recognition mode revealed by the X-ray structure of a core U2AF35/U2AF65 heterodimer. Cell. 2001;106:595-605 pubmed
    ..The X-ray structure of the human core U2AF heterodimer, consisting of the U2AF35 central domain and a proline-rich region of U2AF65, has been determined at 2.2 A resolution...
  9. Ding W, Kuntz S, Miller L. A misspliced form of the cholecystokinin-B/gastrin receptor in pancreatic carcinoma: role of reduced sellular U2AF35 and a suboptimal 3'-splicing site leading to retention of the fourth intron. Cancer Res. 2002;62:947-52 pubmed
    ..Indeed, quantitative real-time PCR demonstrated a reduced level of expression of one of these factors, U2AF35, in pancreatic cancer cells compared with healthy pancreas...

More Information

Publications159 found, 100 shown here

  1. Soares L, Zanier K, Mackereth C, Sattler M, Valcarcel J. Intron removal requires proofreading of U2AF/3' splice site recognition by DEK. Science. 2006;312:1961-5 pubmed
    ..The 65- and 35-kD subunits of the splicing factor U2AF, U2AF65 and U2AF35, recognize, respectively, the pyrimidine-rich tract and the conserved terminal AG present at metazoan 3' splice ..
  2. Pacheco T, Coelho M, Desterro J, Mollet I, Carmo Fonseca M. In vivo requirement of the small subunit of U2AF for recognition of a weak 3' splice site. Mol Cell Biol. 2006;26:8183-90 pubmed
  3. Graubert T, Shen D, Ding L, Okeyo Owuor T, Lunn C, Shao J, et al. Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes. Nat Genet. 2011;44:53-7 pubmed publisher
    ..Here we show that a missense mutation affecting the serine at codon 34 (Ser34) in U2AF1 was recurrently present in 13 out of 150 (8...
  4. Makishima H, Visconte V, Sakaguchi H, Jankowska A, Abu Kar S, Jerez A, et al. Mutations in the spliceosome machinery, a novel and ubiquitous pathway in leukemogenesis. Blood. 2012;119:3203-10 pubmed publisher
    ..We identified additional somatic mutations in spliceosomal genes, including SF3B1, U2AF1, and SRSF2. These mutations alter pre-mRNA splicing patterns...
  5. Thol F, Kade S, Schlarmann C, Löffeld P, Morgan M, Krauter J, et al. Frequency and prognostic impact of mutations in SRSF2, U2AF1, and ZRSR2 in patients with myelodysplastic syndromes. Blood. 2012;119:3578-84 pubmed publisher
    ..In the present study, we examined a cohort of 193 MDS patients for mutations in SRSF2, U2AF1 (synonym U2AF35), ZRSR2, and, as described previously, SF3B1, in the context of other molecular markers, including mutations in ..
  6. Izquierdo J. Fas splicing regulation during early apoptosis is linked to caspase-mediated cleavage of U2AF65. Mol Biol Cell. 2008;19:3299-307 pubmed publisher
    ..The dominant-negative behavior of the U2AF65 N-terminal fragment can be reverted by U2AF35 overexpression...
  7. Janku F, Diamond E, Goodman A, Kandadai Raghavan V, Barnes T, Kato S, et al. Molecular Profiling of Tumor Tissue and Plasma Cell-Free DNA from Patients with Non-Langerhans Cell Histiocytosis. Mol Cancer Ther. 2019;: pubmed publisher
    ..Four patients had JAK2, MPL ASXL1, U2AF1 alterations, which can correlate with myeloid neoplasms, a known ECD predisposition, and one developed ..
  8. McClure R, Ewalt M, Crow J, Temple Smolkin R, Pullambhatla M, Sargent R, et al. Clinical Significance of DNA Variants in Chronic Myeloid Neoplasms: A Report of the Association for Molecular Pathology. J Mol Diagn. 2018;20:717-737 pubmed publisher
    ..KIT, KRAS, MPL, NF1, NPM1, NRAS, PHF6, PPM1D, PTPN11, RAD21, RUNX1, SETBP1, SF3B1, SMC3, SRSF2, STAG2, TET2, TP53, U2AF1, and ZRSR2...
  9. Bartels S, Schipper E, Hasemeier B, Kreipe H, Lehmann U. Routine clinical mutation profiling using next generation sequencing and a customized gene panel improves diagnostic precision in myeloid neoplasms. Oncotarget. 2016;7:30084-93 pubmed publisher
    ..7% up to 95.7%. Most frequently mutated genes were TET2 (28.7%), SRSF2 (19.5%), ASXL1 (8.6%) and U2AF1 (8.1%). The mutation profiling increases the diagnostic precision and adds prognostic information.
  10. Patel B, Przychodzen B, Thota S, Radivoyevitch T, Visconte V, Kuzmanovic T, et al. Genomic determinants of chronic myelomonocytic leukemia. Leukemia. 2017;31:2815-2823 pubmed publisher
    ..In contrast, dysplastic features correlated with mutations usually encountered in MDS (for example, SF3B1 and U2AF1)...
  11. Sun C, Wang J, Zhou X. [Research Progress on Spliceosome Mutations in Hematopoietic Malignancy]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2016;24:925-9 pubmed publisher
    ..review, the structure as well as function of spliceosome are introduced and the common mutations such as SF3B1, U2AF35, SRSF2 and ZRSR2 as well as their frequency, mutation versions, clinical phenotypies and effects on prognosis are ..
  12. Li B, Gale R, Xu Z, Qin T, Song Z, Zhang P, et al. Non-driver mutations in myeloproliferative neoplasm-associated myelofibrosis. J Hematol Oncol. 2017;10:99 pubmed publisher
    ..Fifty-eight subjects had ≥1 non-driver mutation upon diagnosis. Mutations in mRNA splicing genes, especially in U2AF1, were significantly more frequent in PMF than in post-PV/ET MF (33 vs. 6%; P = 0.015)...
  13. Maxson J, Tyner J. Genomics of chronic neutrophilic leukemia. Blood. 2017;129:715-722 pubmed publisher
    ..These commonalities include mutations in SETBP1, spliceosome proteins (SRSF2, U2AF1), and epigenetic modifiers (TET2, ASXL1)...
  14. Smith M, Choudhary G, Pellagatti A, Choi K, Bolanos L, Bhagat T, et al. U2AF1 mutations induce oncogenic IRAK4 isoforms and activate innate immune pathways in myeloid malignancies. Nat Cell Biol. 2019;: pubmed publisher
    ..Expression of IRAK4-L is mediated by mutant U2 small nuclear RNA auxiliary factor 1 (U2AF1) and is associated with oncogenic signalling in MDS and AML...
  15. Leo F, Bartels S, Mägel L, Framke T, Büsche G, Jonigk D, et al. Prognostic factors in the myoepithelial-like spindle cell type of metaplastic breast cancer. Virchows Arch. 2016;469:191-201 pubmed publisher
    ..GNAQ, GNAS, KIT, KRAS, MAP2K1, MET, MSH6, NRAS, PDGFRA, PIK3CA, PTEN, SF3B1, SMAD4, SRC, SRSF2, STK11, TP53, and U2AF1; copy numbers for EGFR, c-myc, FGFR, PLAG, c-met) were assessed...
  16. Lindsley R, Mar B, Mazzola E, Grauman P, Shareef S, Allen S, et al. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood. 2015;125:1367-76 pubmed publisher
    ..The presence of a mutation in SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2 was >95% specific for the diagnosis of s-AML...
  17. Liberante F, Lappin K, Barros E, Vohhodina J, Grebien F, Savage K, et al. Altered splicing and cytoplasmic levels of tRNA synthetases in SF3B1-mutant myelodysplastic syndromes as a therapeutic vulnerability. Sci Rep. 2019;9:2678 pubmed publisher
    ..sequencing efforts have uncovered recurrent somatic mutations within RNA splicing factors, including SF3B1, SRSF2, U2AF1 and ZRSR2. The most frequently mutated gene is SF3B1, mutated in 17% of MDS patients...
  18. Shirai C, Ley J, White B, Kim S, Tibbitts J, Shao J, et al. Mutant U2AF1 Expression Alters Hematopoiesis and Pre-mRNA Splicing In Vivo. Cancer Cell. 2015;27:631-43 pubmed publisher
    Heterozygous somatic mutations in the spliceosome gene U2AF1 occur in ∼ 11% of patients with myelodysplastic syndromes (MDS), the most common adult myeloid malignancy. It is unclear how these mutations contribute to disease...
  19. Eisfeld A, Kohlschmidt J, Mrozek K, Blachly J, Walker C, Nicolet D, et al. Mutation patterns identify adult patients with de novo acute myeloid leukemia aged 60 years or older who respond favorably to standard chemotherapy: an analysis of Alliance studies. Leukemia. 2018;32:1338-1348 pubmed publisher
    ..RAS pathway genes, FLT3-TKD, and/or patients without FLT3-ITD) achieved a CR, only 32% of poor-risk patients (with U2AF1, WT1 mutations and/or complex karyotype) did. Intermediate-risk patients had a 50% CR rate...
  20. Zahid M, Patnaik M, Gangat N, Hashmi S, Rizzieri D. Insight into the molecular pathophysiology of myelodysplastic syndromes: targets for novel therapy. Eur J Haematol. 2016;97:313-20 pubmed publisher
    ..interferon-gamma, SMAD proteins), mutations in genes encoding the RNA splicing machinery (SF3B1, SRSF2, ZRSR2, and U2AF1 genes), mutations in genes disrupting the epigenetic machinery (TET2, DNMT3A, DNMT3B, EZH2, ASXL1)...
  21. Fei D, Zhen T, Durham B, Ferrarone J, Zhang T, Garrett L, et al. Impaired hematopoiesis and leukemia development in mice with a conditional knock-in allele of a mutant splicing factor gene U2af1. Proc Natl Acad Sci U S A. 2018;115:E10437-E10446 pubmed publisher
    Mutations affecting the spliceosomal protein U2AF1 are commonly found in myelodysplastic syndromes (MDS) and secondary acute myeloid leukemia (sAML)...
  22. Wu T, Fu X. Genomic functions of U2AF in constitutive and regulated splicing. RNA Biol. 2015;12:479-85 pubmed publisher
    ..Given prevalent mutations in U2AF, particularly in the U2AF1 gene (which encodes for the U2AF35 subunit) in blood disorders and other human cancers, there are renewed interests in these classic splicing factors ..
  23. Tian J, Zhu B, Tian Y, Zhong R, Miao X, Wang L. [Association between pancreatic cancer risk and the interaction of U2AF65 gene polymorphisms and smoking]. Zhonghua Liu Xing Bing Xue Za Zhi. 2014;35:710-3 pubmed
    To determine the association between U2 small nuclear ribonucleoprotein auxiliary factor 35/65 (U2AF35 and U2AF65) and pancreatic cancer (PC). A two-stage analysis case-control study was conducted...
  24. Kim S, Park C, Jun Y, Lee S, Jung Y, Kim J. Integrative Profiling of Alternative Splicing Induced by U2AF1 S34F Mutation in Lung Adenocarcinoma Reveals a Mechanistic Link to Mitotic Stress. Mol Cells. 2018;41:733-741 pubmed publisher
    ..One of the most frequently found is U2AF1 S34F missense mutation...
  25. Wang J, Ma J, Lin Y, Wang J, Shen H, Gui F, et al. [Mutational analysis of RNA splicing machinery genes SF3B1, U2AF1 and SRSF2 in 118 patients with myelodysplastic syndromes and related diseases]. Zhonghua Xue Ye Xue Za Zhi. 2017;38:192-197 pubmed publisher
    ..Mutational analysis of splicing factor 3B subunit 1 (SF3B1) (K700E) , U2 small nuclear RNA auxiliary factor 1 (U2AF1) (S34, Q157P) and serine/arginine-rich splicing factor 2 (SRSF2) (P95) in 118, de novo MDS and related diseases ..
  26. Xu J, Smeets M, Tan S, Wall M, Purton L, Walkley C. Modeling human RNA spliceosome mutations in the mouse: not all mice were created equal. Exp Hematol. 2019;70:10-23 pubmed publisher
    ..genome identified recurrent heterozygous mutations in the RNA splicing machinery, with the SF3B1, SRSF2, and U2AF1 genes being frequently mutated...
  27. Tamari R, Rapaport F, Zhang N, McNamara C, Kuykendall A, Sallman D, et al. Impact of High-Molecular-Risk Mutations on Transplantation Outcomes in Patients with Myelofibrosis. Biol Blood Marrow Transplant. 2019;: pubmed publisher
    ..The presence of U2AF1 (P = .007) or DNMT3A (P = .034) mutations was associated with worse OS...
  28. Schulz R, McCole R, Woodfine K, Wood A, Chahal M, Monk D, et al. Transcript- and tissue-specific imprinting of a tumour suppressor gene. Hum Mol Genet. 2009;18:118-27 pubmed publisher
    ..of Nnat in brain, as has been suggested previously for the similarly organized and imprinted murine Commd1/U2af1-rs1 locus...
  29. Parra M, Booth B, Weiszmann R, Yee B, Yeo G, Brown J, et al. An important class of intron retention events in human erythroblasts is regulated by cryptic exons proposed to function as splicing decoys. RNA. 2018;24:1255-1265 pubmed publisher
    ..Although many of these cryptic exons were spliced inefficiently, they exhibited substantial binding of U2AF1 and U2AF2 adjacent to their splice acceptor sites...
  30. Brooks A, Choi P, de Waal L, Sharifnia T, Imielinski M, Saksena G, et al. A pan-cancer analysis of transcriptome changes associated with somatic mutations in U2AF1 reveals commonly altered splicing events. PLoS ONE. 2014;9:e87361 pubmed publisher
    Although recurrent somatic mutations in the splicing factor U2AF1 (also known as U2AF35) have been identified in multiple cancer types, the effects of these mutations on the cancer transcriptome have yet to be fully elucidated...
  31. Heuser M, Gabdoulline R, Löffeld P, Dobbernack V, Kreimeyer H, Pankratz M, et al. Individual outcome prediction for myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia from MDS after allogeneic hematopoietic cell transplantation. Ann Hematol. 2017;96:1361-1372 pubmed publisher
    ..In multivariate analysis, mutated NRAS, U2AF1, IDH2, and TP53 and/or a complex karyotype were significant prognostic markers for OS besides age above 60 years, ..
  32. Adams D, van der Weyden L, Mayeda A, Stamm S, Morris B, Rasko J. ZNF265--a novel spliceosomal protein able to induce alternative splicing. J Cell Biol. 2001;154:25-32 pubmed
    ..Alignment with other RS domain-containing proteins revealed a high degree of SR dipeptide conservation. These data show that ZNF265 functions as a novel component of the mRNA processing machinery. ..
  33. Kang M, Kim H, Seo B, Lee J, Choi S, Kim S, et al. The prognostic impact of mutations in spliceosomal genes for myelodysplastic syndrome patients without ring sideroblasts. BMC Cancer. 2015;15:484 pubmed publisher
    ..of 129 de novo MDS patients, who did not harbor RS, for mutations affecting three spliceosomal genes (SF3B1, U2AF1, and SRSF2). The mutation rates of SF3B1, U2AF1, and SRSF2 were 7.0 %, 7.8 %, and 10.1 %, respectively...
  34. Hong W, Bennett M, Xiao Y, Feld Kramer R, Wang C, Reed R. Association of U2 snRNP with the spliceosomal complex E. Nucleic Acids Res. 1997;25:354-61 pubmed
    ..However, we find that U2 snRNP is not as tightly bound in the E complex as it is in the A complex. The possible significance of the weak association of U2 snRNP with the E complex is discussed. ..
  35. Choi H, Kim H, Baek H, Kook H, Cho D, Shin J, et al. Alteration of the SETBP1 gene and splicing pathway genes SF3B1, U2AF1, and SRSF2 in childhood acute myeloid leukemia. Ann Lab Med. 2015;35:118-22 pubmed publisher
    ..possible alteration of the SETBP1, splicing factor 3B subunit 1 (SF3B1), U2 small nuclear RNA auxiliary factor 1 (U2AF1), and serine/arginine-rich splicing factor 2 (SRSF2) genes in childhood AML...
  36. Schreiber C, Sakuma T, Izumiya Y, Holditch S, Hickey R, Bressin R, et al. An siRNA Screen Identifies the U2 snRNP Spliceosome as a Host Restriction Factor for Recombinant Adeno-associated Viruses. PLoS Pathog. 2015;11:e1005082 pubmed publisher
    ..Genetic disruption of U2 snRNP and associated proteins, such as SF3B1 and U2AF1, also increased expression from AAV vector, suggesting the critical role of U2 snRNP spliceosome complex in this ..
  37. Li L, Xiao Z, Sun X. [Role of Aberrant Splicing in Pathogenesis of Myelodysplastic Syndromes-Review]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2017;25:617-621 pubmed publisher
    ..Recently, it was reported that the mutated or dysregulated splicing factors, including SF3B1, SRSF2 and U2AF1, attribute to aberrant mRNA splicing, which leads to hematopoietic dysfunction and drives MDS...
  38. Maréchal D, Lopes Pereira P, Duchon A, Herault Y. Dosage of the Abcg1-U2af1 region modifies locomotor and cognitive deficits observed in the Tc1 mouse model of Down syndrome. PLoS ONE. 2015;10:e0115302 pubmed publisher
    ..report we analyzed the contribution of the genetic dosage of 13 conserved mouse genes located between Abcg1 and U2af1, in the telomeric part of Hsa21...
  39. Kralovicova J, Knut M, Cross N, Vorechovsky I. Identification of U2AF(35)-dependent exons by RNA-Seq reveals a link between 3' splice-site organization and activity of U2AF-related proteins. Nucleic Acids Res. 2015;43:3747-63 pubmed publisher
    ..The gene encoding U2AF35 (U2AF1) is alternatively spliced, giving rise to two isoforms U2AF35a and U2AF35b...
  40. Hamilton B, Visconte V, Jia X, Tabarroki A, Makishima H, Hasrouni E, et al. Impact of allogeneic hematopoietic cell transplant in patients with myeloid neoplasms carrying spliceosomal mutations. Am J Hematol. 2016;91:406-9 pubmed publisher
    ..Mutations in the spliceosomal genes (U2AF1 and SRSF2) predict for poor outcomes in myelodysplastic syndromes (MDS) and related diseases...
  41. Yang Y, Chiu Y, Kao C, Hou H, Lin C, Tsai C, et al. The prognostic significance of global aberrant alternative splicing in patients with myelodysplastic syndrome. Blood Cancer J. 2018;8:78 pubmed publisher
    ..A higher degree of global aberrant AS was associated with male gender and U2AF1 mutation, and predicted shorter overall survival and time to leukemic change...
  42. Shirahata Adachi M, Iriyama C, Tomita A, Suzuki Y, Shimada K, Kiyoi H. Altered EZH2 splicing and expression is associated with impaired histone H3 lysine 27 tri-Methylation in myelodysplastic syndrome. Leuk Res. 2017;63:90-97 pubmed publisher
    ..EZH2 expression was observed in patients with or without alterations in genes involved with RNA splicing, SRSF2, U2AF1 and SF3B1...
  43. Zhao P, Liang J, Deng Z, Wang M, Qin J, Chen C, et al. Association of Gene Mutations with Response to Arsenic-Containing Compound Qinghuang Powder () in Patients with Myelodysplastic Syndromes. Chin J Integr Med. 2018;: pubmed publisher
    ..The most common mutations were in SF3B1, U2AF1, ASXL1, and DNMT3A. After treatment with CQHP, about 88...
  44. Hsu T, Simon L, Neill N, Marcotte R, Sayad A, Bland C, et al. The spliceosome is a therapeutic vulnerability in MYC-driven cancer. Nature. 2015;525:384-8 pubmed publisher
    ..Core spliceosomal factors (such as SF3B1 and U2AF1) associated with BUD31 are also required to tolerate oncogenic MYC...
  45. JakubauskienÄ— E, Peciuliene I, Vilys L, Mocevicius P, Vilkaitis G, Kanopka A. Gastrointestinal tract tumors and cell lines possess differential splicing factor expression and tumor associated mRNA isoform formation profiles. Cancer Biomark. 2015;15:575-81 pubmed publisher
    ..We present experimental evidence that splicing factor SRSF1, SRSF2, U2AF35, U2AF65 and KHSRP expression levels in gastrointestinal tract (colon, gastric and pancreatic) tumors differ ..
  46. Eisfeld A, Kohlschmidt J, Mrozek K, Blachly J, Nicolet D, Kroll K, et al. Adult acute myeloid leukemia with trisomy 11 as the sole abnormality is characterized by the presence of five distinct gene mutations: MLL-PTD, DNMT3A, U2AF1, FLT3-ITD and IDH2. Leukemia. 2016;30:2254-2258 pubmed publisher
  47. Tefferi A, Lasho T, Patnaik M, Saeed L, Mudireddy M, Idossa D, et al. Targeted next-generation sequencing in myelodysplastic syndromes and prognostic interaction between mutations and IPSS-R. Am J Hematol. 2017;92:1311-1317 pubmed publisher
    ..The most frequent mutations/variants included ASXL1 (30%), TET2 (25%), SF3B1 (20%), U2AF1 (16%), SRSF2 (16%), TP53 (13%), RUNX1 (11%), and DNMT3A (10%)...
  48. Chen L, Chen J, Huang Y, Gu Y, Qiu J, Qian H, et al. The Augmented R-Loop Is a Unifying Mechanism for Myelodysplastic Syndromes Induced by High-Risk Splicing Factor Mutations. Mol Cell. 2018;69:412-425.e6 pubmed publisher
    ..a chain of events triggered by multiple splicing factor mutations, especially high-risk alleles in SRSF2 and U2AF1, including elevated R-loops, replication stress, and activation of the ataxia telangiectasia and Rad3-related ..
  49. Ping N, Sun A, Song Y, Wang Q, Yin J, Cheng W, et al. Exome sequencing identifies highly recurrent somatic GATA2 and CEBPA mutations in acute erythroid leukemia. Leukemia. 2017;31:195-202 pubmed publisher
    ..7%), GATA2 (22.4%), NPM1 (15.5%), SETBP1 (12.1%) and U2AF1 (12.1%)...
  50. Pellagatti A, Armstrong R, Steeples V, Sharma E, Repapi E, Singh S, et al. Impact of spliceosome mutations on RNA splicing in myelodysplasia: dysregulated genes/pathways and clinical associations. Blood. 2018;: pubmed publisher
    SF3B1, SRSF2 and U2AF1 are the most frequently mutated splicing factor genes in the myelodysplastic syndromes (MDS)...
  51. Xiao S, Manley J. Phosphorylation-dephosphorylation differentially affects activities of splicing factor ASF/SF2. EMBO J. 1998;17:6359-67 pubmed
    ..We discuss these results with respect to the differential protein-protein interactions that must occur during constitutive and activated splicing. ..
  52. McCole R, Loughran N, Chahal M, Fernandes L, Roberts R, Fraternali F, et al. A case-by-case evolutionary analysis of four imprinted retrogenes. Evolution. 2011;65:1413-27 pubmed publisher
    ..examine the evolutionary fate of four retrogenes generated by such an event; mouse Inpp5f_v2, Mcts2, Nap1l5, and U2af1-rs1. These genes are all subject to the epigenetic phenomenon of parental imprinting...
  53. Kim J, Chung I. The splicing factor U2AF65 stabilizes TRF1 protein by inhibiting its ubiquitin-dependent proteolysis. Biochem Biophys Res Commun. 2014;443:1124-30 pubmed publisher
    ..Hence, U2AF65 represents a new route for modulating TRF1 function at telomeres. ..
  54. Guth S, Tange T, Kellenberger E, Valcarcel J. Dual function for U2AF(35) in AG-dependent pre-mRNA splicing. Mol Cell Biol. 2001;21:7673-81 pubmed
  55. Wassie E, Finke C, Gangat N, Lasho T, Pardanani A, Hanson C, et al. A compendium of cytogenetic abnormalities in myelofibrosis: molecular and phenotypic correlates in 826 patients. Br J Haematol. 2015;169:71-6 pubmed publisher
    ..A proportion of patients were also screened for ASXL1, EZH2, IDH1, IDH2, SRSF2, U2AF1 and SF3B1 mutations; in all instances, mutational frequencies were higher in patients with normal karyotype, ..
  56. Hou H, Liu C, Kuo Y, Chou W, Tsai C, Lin C, et al. Splicing factor mutations predict poor prognosis in patients with de novo acute myeloid leukemia. Oncotarget. 2016;7:9084-101 pubmed publisher
    ..In this study, we investigated mutations of three SF genes, SF3B1, U2AF1 and SRSF2, by Sanger sequencing in 500 patients with de novo AML and analysed their clinical relevance...
  57. Cavalcanti M, Schultheis A, Ho C, Wang L, Delair D, Weigelt B, et al. Mixed Mesonephric Adenocarcinoma and High-grade Neuroendocrine Carcinoma of the Uterine Cervix: Case Description of a Previously Unreported Entity With Insights Into Its Molecular Pathogenesis. Int J Gynecol Pathol. 2017;36:76-89 pubmed publisher
    ..Both components shared identical mutations in U2AF1 p.R156H (c.467G>A) and GATA3 p.M422fs (c.1263dupG), as well as MYCN amplification...
  58. Maita H, Kitaura H, Ariga H, Iguchi Ariga S. CIR, a corepressor of CBF1, binds to PAP-1 and effects alternative splicing. Exp Cell Res. 2005;303:375-87 pubmed
    ..their subcellular localizations and interactions with PAP-1 and other SR proteins, including SC35, SF2/ASF, and U2AF35. CIR was found to interact with U2AF35 through the BA domain, with SC35 and SF2/ASF through the RS domain, and ..
  59. Hong J, Seo J, Kim S, Jung H, Park S, Kim K, et al. Mutations in the Spliceosomal Machinery Genes SRSF2, U2AF1, and ZRSR2 and Response to Decitabine in Myelodysplastic Syndrome. Anticancer Res. 2015;35:3081-9 pubmed
    ..In recent years, novel recurrent mutations in multiple genes encoding RNA spliceosomal machinery (SRSF2, U2AF1, ZRSR2, SF3B1) were revealed...
  60. Kröger N, Panagiota V, Badbaran A, Zabelina T, Triviai I, Araujo Cruz M, et al. Impact of Molecular Genetics on Outcome in Myelofibrosis Patients after Allogeneic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2017;23:1095-1101 pubmed publisher
    ..calreticulin (n = 34), SRSF2 (n = 16), TET2 (n = 10), U2AF1 (n = 11), EZH2 (n = 7), MPL (n = 6), IDH2 (n = 5), IDH1 (n..
  61. Will C, Schneider C, MacMillan A, Katopodis N, Neubauer G, Wilm M, et al. A novel U2 and U11/U12 snRNP protein that associates with the pre-mRNA branch site. EMBO J. 2001;20:4536-46 pubmed
    ..Immuno precipitations indicated that p14 is present in U12-type spliceosomes, consistent with the idea that branch point selection is similar in the major and minor spliceosomes. ..
  62. Zhou J, Zhang T, Wang Y, Yang D, Yang L, Ma J, et al. DLX4 hypermethylation is a prognostically adverse indicator in de novo acute myeloid leukemia. Tumour Biol. 2016;37:8951-60 pubmed publisher
    ..DLX4 methylated patients showed significantly higher frequency of U2AF1 mutation compared with DLX4 unmethylated patients (P = 0.043)...
  63. Patnaik M, Lasho T, Finke C, Hanson C, Hodnefield J, Knudson R, et al. Spliceosome mutations involving SRSF2, SF3B1, and U2AF35 in chronic myelomonocytic leukemia: prevalence, clinical correlates, and prognostic relevance. Am J Hematol. 2013;88:201-6 pubmed publisher
    SRSF2, SF3B1, and U2AF35 (U2AF1) are the three most frequent genes involved with spliceosome mutations in myeloid malignancies...
  64. Rino J, Desterro J, Pacheco T, Gadella T, Carmo Fonseca M. Splicing factors SF1 and U2AF associate in extraspliceosomal complexes. Mol Cell Biol. 2008;28:3045-57 pubmed publisher
    ..We propose that SF1 and U2AF form extraspliceosomal complexes before and after taking part in the assembly of catalytic spliceosomes. ..
  65. Przychodzen B, Jerez A, Guinta K, Sekeres M, Padgett R, Maciejewski J, et al. Patterns of missplicing due to somatic U2AF1 mutations in myeloid neoplasms. Blood. 2013;122:999-1006 pubmed publisher
    ..One of these spliceosomal genes, U2AF1, was affected by canonical somatic mutations in aggressive type of myeloid malignancies...
  66. Whisenant T, Peralta E, Aarreberg L, Gao N, Head S, Ordoukhanian P, et al. The Activation-Induced Assembly of an RNA/Protein Interactome Centered on the Splicing Factor U2AF2 Regulates Gene Expression in Human CD4 T Cells. PLoS ONE. 2015;10:e0144409 pubmed publisher
    ..the PIM, SYNCRIP, impacts a limited but immunologically important set of U2AF2-bound transcripts, knockdown of U2AF1 significantly impairs assembly of the majority of protein and mRNA components in the activation-induced ..
  67. Kahles A, Lehmann K, Toussaint N, Hüser M, Stark S, Sachsenberg T, et al. Comprehensive Analysis of Alternative Splicing Across Tumors from 8,705 Patients. Cancer Cell. 2018;: pubmed publisher
    ..of somatic variants with alternative splicing events confirmed known trans associations with variants in SF3B1 and U2AF1 and identified additional trans-acting variants (e.g., TADA1, PPP2R1A)...
  68. Vinayanuwattikun C, Le Calvez Kelm F, Abedi Ardekani B, Zaridze D, Mukeria A, Voegele C, et al. Elucidating Genomic Characteristics of Lung Cancer Progression from In Situ to Invasive Adenocarcinoma. Sci Rep. 2016;6:31628 pubmed publisher
    ..32% TCGA), while a higher number of mutations of RNA-splicing genes, RBM10 and U2AF1, were found (37% vs. 11% TCGA)...
  69. Ellis J, Llères D, Denegri M, Lamond A, Cáceres J. Spatial mapping of splicing factor complexes involved in exon and intron definition. J Cell Biol. 2008;181:921-34 pubmed publisher
    ..snRNP)-associated 70-kD protein (U1 70K) and with the small subunit of the U2 snRNP auxiliary factor (U2AF35) in live-cell nuclei...
  70. Nguyen H, Leong W, Li W, Reddy P, Sullivan J, Walter M, et al. Spliceosome Mutations Induce R Loop-Associated Sensitivity to ATR Inhibition in Myelodysplastic Syndromes. Cancer Res. 2018;78:5363-5374 pubmed publisher
    Heterozygous somatic mutations in spliceosome genes (U2AF1, SF3B1, ZRSR2, or SRSF2) occur in >50% of patients with myelodysplastic syndrome (MDS)...
  71. Wong F, Boo N, Ainoon O, Wang M. Variants of organic anion transporter polypeptide 2 gene are not risk factors associated with severe neonatal hyperbilirubinemia. Malays J Pathol. 2009;31:99-104 pubmed
    ..Variants of OATP2 gene were not significant risk factors associated with severe hyperbilirubinemia in Malaysian Chinese infants. ..
  72. Qian J, Yao D, Lin J, Qian W, Wang C, Chai H, et al. U2AF1 mutations in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome. PLoS ONE. 2012;7:e45760 pubmed publisher
    Somatic mutations of U2AF1 gene have recently been identified in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML)...
  73. Berman E, Jhanwar S, Hedvat C, Arcila M, Wahab O, Levine R, et al. Resistance to imatinib in patients with chronic myelogenous leukemia and the splice variant BCR-ABL1(35INS). Leuk Res. 2016;49:108-12 pubmed publisher
    ..DNA sequencing of commonly mutated spliceosomal genes SF3B1, U2AF1, SRSF2, ZRSR2, SFA31, PRPF408, U2A565, and SF1 did not reveal mutations in seven BCR-ABL1(35INS) -positive ..
  74. Engle E, Fisher D, Miller C, McLellan M, Fulton R, Moore D, et al. Clonal evolution revealed by whole genome sequencing in a case of primary myelofibrosis transformed to secondary acute myeloid leukemia. Leukemia. 2015;29:869-76 pubmed publisher
    ..The first group (including JAK2 and U2AF1), representing the founding clone, included mutations with high frequency at all three disease stages...
  75. Bejar R. Splicing Factor Mutations in Cancer. Adv Exp Med Biol. 2016;907:215-28 pubmed publisher
    ..The most frequent mutations occur in SF3B1, U2AF1, SRSF2, and ZRSR2 and are largely exclusive of each other...
  76. Horiuchi K, Perez Cerezales S, Papasaikas P, Ramos Ibeas P, López Cardona A, Laguna Barraza R, et al. Impaired Spermatogenesis, Muscle, and Erythrocyte Function in U12 Intron Splicing-Defective Zrsr1 Mutant Mice. Cell Rep. 2018;23:143-155 pubmed publisher
    The U2AF35-like ZRSR1 has been implicated in the recognition of 3' splice site during spliceosome assembly, but ZRSR1 knockout mice do not show abnormal phenotypes...
  77. Ivanova M, Shivarov V, Pavlov I, Lilakos K, Naumova E. Clinical Evaluation of a Novel Nine-Gene Panel for Ion Torrent PGM Sequencing of Myeloid Malignancies. Mol Diagn Ther. 2016;20:27-32 pubmed
    ..of the exonic regions of nine human genes as follows: ASXL1, EZH2, CALR, RUNX1, SETBP1, SF3B1, SRSF2, TET2, and U2AF1. Initial testing of the panel performance was performed on an Ion PGM(â„¢) machine using PGM(â„¢) 316 v2 ..
  78. Stepanyuk G, Serrano P, Peralta E, Farr C, Axelrod H, Geralt M, et al. UHM-ULM interactions in the RBM39-U2AF65 splicing-factor complex. Acta Crystallogr D Struct Biol. 2016;72:497-511 pubmed publisher
    ..When compared with related complexes, such as U2AF35-U2AF65 and RBM39-SF3b155, the RBM39-UHM-U2AF65-ULM complex reveals both common and discriminating recognition ..
  79. Sun Q, Ding L, Tan K, Chien W, Mayakonda A, Lin D, et al. Ordering of mutations in acute myeloid leukemia with partial tandem duplication of MLL (MLL-PTD). Leukemia. 2017;31:1-10 pubmed publisher
    ..Genes involved in the cohesin complex (STAG2), a splicing factor (U2AF1) and a poorly studied gene, MGA were recurrently mutated, whereas NPM1, one of the most frequently mutated AML ..
  80. Delic S, Rose D, Kern W, Nadarajah N, Haferlach C, Haferlach T, et al. Application of an NGS-based 28-gene panel in myeloproliferative neoplasms reveals distinct mutation patterns in essential thrombocythaemia, primary myelofibrosis and polycythaemia vera. Br J Haematol. 2016;175:419-426 pubmed publisher
    ..Moreover, significantly more mutated splicing genes (SF3B1, SRSF2 and U2AF1) were present in PMF (0·60 mutated genes/patient) compared to ET (0·15) while no mutations in splicing genes ..
  81. Chen L, Weinmeister R, Kralovicova J, Eperon L, Vorechovsky I, Hudson A, et al. Stoichiometries of U2AF35, U2AF65 and U2 snRNP reveal new early spliceosome assembly pathways. Nucleic Acids Res. 2017;45:2051-2067 pubmed publisher
    ..We have used single molecule methods to test whether the major components implicated in selection, the proteins U2AF35 and U2AF65 and the U2 snRNP, are able to recognize alternative candidate sites or are restricted to one pre-..
  82. Nayler O, Stratling W, Bourquin J, Stagljar I, Lindemann L, Jasper H, et al. SAF-B protein couples transcription and pre-mRNA splicing to SAR/MAR elements. Nucleic Acids Res. 1998;26:3542-9 pubmed
  83. Zolotukhin A, Tan W, Bear J, Smulevitch S, Felber B. U2AF participates in the binding of TAP (NXF1) to mRNA. J Biol Chem. 2002;277:3935-42 pubmed
    ..screens and in vitro binding studies, we found that this region coincides with a direct binding site for U2AF35, the small subunit of the splicing factor U2AF...
  84. Tefferi A, Finke C, Lasho T, Wassie E, Knudson R, Ketterling R, et al. U2AF1 mutations in primary myelofibrosis are strongly associated with anemia and thrombocytopenia despite clustering with JAK2V617F and normal karyotype. Leukemia. 2014;28:431-3 pubmed publisher
  85. Dao K, Tyner J. What's different about atypical CML and chronic neutrophilic leukemia?. Hematology Am Soc Hematol Educ Program. 2015;2015:264-71 pubmed publisher
    ..We also report a novel finding-our study reveals a high frequency of U2AF1 mutations at codon Q157 associated with CSF3R mutant myeloid neoplasms...
  86. Rudner D, Kanaar R, Breger K, Rio D. Interaction between subunits of heterodimeric splicing factor U2AF is essential in vivo. Mol Cell Biol. 1998;18:1765-73 pubmed
    ..These data indicate that Drosophila U2AF heterodimer formation is essential for viability in vivo, consistent with a requirement for both subunits in splicing in vitro. ..
  87. Hwang S, Kim S, Kim J, Park H, Park S, Im K, et al. Short telomere length and its correlation with gene mutations in myelodysplastic syndrome. J Hematol Oncol. 2016;9:62 pubmed publisher
    ..021), and this was an independent prognostic factor, along with TP53, U2AF1 mutation, and high BM blast count (P?=?0.044, 0.001, 0.004, 0.012, respectively)...
  88. Cheng H, Liu S, Liu Y, Zhao X, Li W, Qiu L, et al. [Application of Next Generation Sequencing for AML/MDS Diagnosis and Treatment]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2017;25:1631-1635 pubmed publisher
    ..The gene mutations were as follows: CEBPA (11.8%), DNMT3A (7.4%), C-KIT (7.4%) and FLT3-ITD (7.4%) in AML, and U2AF1 (10.5%) and SRSF2 (10.5%) in MDS. All the genes had specific mutation sites except TP53 and CEBPA...
  89. Je E, Yoo N, Kim Y, Kim M, Lee S. Mutational analysis of splicing machinery genes SF3B1, U2AF1 and SRSF2 in myelodysplasia and other common tumors. Int J Cancer. 2013;133:260-5 pubmed publisher
    Recurrent somatic mutations in splicing machinery components, including SF3B1, U2AF1 and SRSF2 genes have recently been reported in myelodysplastic syndromes (MDS)...
  90. Kralovicova J, Knut M, Cross N, Vorechovsky I. Exon-centric regulation of ATM expression is population-dependent and amenable to antisense modification by pseudoexon targeting. Sci Rep. 2016;6:18741 pubmed publisher
    ..NSE levels were deregulated in leukemias and were influenced by the identity of U2AF35 residue 34...
  91. Nesic D, Kramer A. Domains in human splicing factors SF3a60 and SF3a66 required for binding to SF3a120, assembly of the 17S U2 snRNP, and prespliceosome formation. Mol Cell Biol. 2001;21:6406-17 pubmed
    ..Finally, we demonstrate that all domains required for interactions within the SF3a heterotrimer and the formation of the 17S U2 snRNP are also necessary to assemble the prespliceosome. ..
  92. Park H, Lee K, Jang Y, Kim S, Thu M, Lee J, et al. The Arabidopsis splicing factors, AtU2AF65, AtU2AF35, and AtSF1 shuttle between nuclei and cytoplasms. Plant Cell Rep. 2017;36:1113-1123 pubmed publisher
    ..The U2AF65 proteins are splicing factors that interact with SF1 and U2AF35 proteins to promote U2snRNP for the recognition of the pre-mRNA 3' splice site during early spliceosome assembly...