The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

U2AF1  -  U2 small nuclear RNA auxiliary factor 1

Homo sapiens

Synonyms: FP793, RN, RNU2AF1, Splicing factor U2AF 35 kDa subunit, U2 auxiliary factor 35 kDa subunit, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of U2AF1

  • As U2AF1 associates with a number of different factors during mRNA splicing, overexpression in trisomy 21 individuals could contribute to some Down syndrome phenotypes by interfering with the splicing process [1].
  • 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 [2].
  • Here we show that U2AF35 appears to be completely dispensable for splicing in nuclear extracts prepared from adenovirus late-infected cells (Ad-NE) [3].
  • These results demonstrated that PAH and IUGR could be mediated by feto-placental hRN through its permeability to the maternal circulation, not by feto-placental hANG production [4].
  • Selected phage clones displayed a peptide RVPPRYHAKISPMVN (called RN-peptide) on their surface [5].

High impact information on U2AF1

  • A novel peptide recognition mode revealed by the X-ray structure of a core U2AF35/U2AF65 heterodimer [6].
  • Our results demonstrate a new biochemical activity of U2AF35, identify the factor that initially recognizes the 3' splice site, and explain why the AG dinucleotide is required for the first step of splicing for some but not all introns [7].
  • Here we use site-specific crosslinking to show that very early during spliceosome assembly U2AF35 directly contacts the 3' splice site [7].
  • U2AF65 binds to RNA at the polypyrimidine tract, whereas U2AF35 is thought to interact through its arginine/serine-rich (RS) domain with other RS-domain-containing factors bound at the 5' splice site, assembled in splicing enhancer complexes, or associated with the U4/U6.U5 small nuclear ribonucleoprotein complex [8].
  • The splicing factor U2AF (U2 snRNP auxiliary factor) is a heterodimer with subunits of 65 and 35 kD (U2AF65 and U2AF35) [9].

Biological context of U2AF1


Anatomical context of U2AF1

  • Both U2AF65 and U2AF35 are concentrated in a small number of nuclear foci corresponding to coiled bodies, subnuclear organelles first identified by light microscopy in 1903 [13].
  • Using two different approaches for measuring FRET, we have identified and spatially localized sites of direct interaction between U2AF35 and U2AF65 in vivo in live cell nuclei [11].

Associations of U2AF1 with chemical compounds

  • 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 [6].
  • The structure reveals a novel protein-protein recognition strategy, in which an atypical RNA recognition motif (RRM) of U2AF35 and the U2AF65 polyproline segment interact via reciprocal "tongue-in-groove" tryptophan residues [6].
  • In this model, recruitment requires interactions between the SR proteins and the 35-kDa subunit of U2AF (U2AF35) [14].
  • U2 snRNP Auxiliary Factor (U2AF) is an essential pre-mRNA splicing factor complex, comprising 35-kDa (U2AF35) and 65-kDa (U2AF65) subunits [11].
  • 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 sites [15].

Physical interactions of U2AF1

  • FRET analyses of the U2AF complex localize the U2AF35/U2AF65 interaction in vivo and reveal a novel self-interaction of U2AF35 [11].

Other interactions of U2AF1

  • 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 [2].
  • We further found in human cells that the exogenously expressed large U2AF subunit, U2AF65, accumulates in spliced mRNP, leading to the recruitment of U2AF35 and TAP [10].
  • The molecular cloning of a 4.1 cDNA encoding the isoform designated 4.1E has allowed us to show that this protein is targeted to the nucleus, that it associates with the splicing factor U2AF35, and that its overexpression induces the redistribution of the splicing factor SC35 [16].
  • 3. One trapped sequence showed complete homology with the cDNA of human U2AF35 (M96982; HGM-approved nomenclature U2AF1), which encodes for the small 35-kDa subunit of the U2 snRNP auxiliary factor [1].
  • DEK phosphorylated at serines 19 and 32 associates with U2AF35, facilitates the U2AF35-AG interaction and prevents binding of U2AF65 to pyrimidine tracts not followed by AG [15].

Analytical, diagnostic and therapeutic context of U2AF1

  • In order to evaluate the resolution of this RH panel, we have now constructed a radiation hybrid map of the Chromosome (Chr) 15q2.3-q2.6 region containing the RN gene [17].


  1. The gene for human U2 snRNP auxiliary factor small 35-kDa subunit (U2AF1) maps to the progressive myoclonus epilepsy (EPM1) critical region on chromosome 21q22.3. Lalioti, M.D., Gos, A., Green, M.R., Rossier, C., Morris, M.A., Antonarakis, S.E. Genomics (1996) [Pubmed]
  2. 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. Ding, W.Q., Kuntz, S.M., Miller, L.J. Cancer Res. (2002) [Pubmed]
  3. Substrate-dependent differences in U2AF requirement for splicing in adenovirus-infected cell extracts. Lützelberger, M., Backström, E., Akusjärvi, G. J. Biol. Chem. (2005) [Pubmed]
  4. Differential roles of renin and angiotensinogen in the feto-maternal interface in the development of complications of pregnancy. Takimoto-Ohnishi, E., Saito, T., Ishida, J., Ohnishi, J., Sugiyama, F., Yagami, K., Fukamizu, A. Mol. Endocrinol. (2005) [Pubmed]
  5. Identification of pentadecapeptide mimicking muramyl peptide. Laman, A.G., Shepelyakovskaya, A.O., Berezin, I.A., Boziev, K.M., Rodionov, I.L., Chulina, I.A., Malakhova, G.V., Brovko, F.A., Murashev, A.N., Korpela, T.K., Nesmeyanov, V.A. Vaccine (2007) [Pubmed]
  6. A novel peptide recognition mode revealed by the X-ray structure of a core U2AF35/U2AF65 heterodimer. Kielkopf, C.L., Rodionova, N.A., Green, M.R., Burley, S.K. Cell (2001) [Pubmed]
  7. Functional recognition of the 3' splice site AG by the splicing factor U2AF35. Wu, S., Romfo, C.M., Nilsen, T.W., Green, M.R. Nature (1999) [Pubmed]
  8. A protein related to splicing factor U2AF35 that interacts with U2AF65 and SR proteins in splicing of pre-mRNA. Tronchère, H., Wang, J., Fu, X.D. Nature (1997) [Pubmed]
  9. The splicing factor U2AF35 mediates critical protein-protein interactions in constitutive and enhancer-dependent splicing. Zuo, P., Maniatis, T. Genes Dev. (1996) [Pubmed]
  10. U2AF participates in the binding of TAP (NXF1) to mRNA. Zolotukhin, A.S., Tan, W., Bear, J., Smulevitch, S., Felber, B.K. J. Biol. Chem. (2002) [Pubmed]
  11. FRET analyses of the U2AF complex localize the U2AF35/U2AF65 interaction in vivo and reveal a novel self-interaction of U2AF35. Chusainow, J., Ajuh, P.M., Trinkle-Mulcahy, L., Sleeman, J.E., Ellenberg, J., Lamond, A.I. RNA (2005) [Pubmed]
  12. Identification and cDNA cloning of a novel RNA-binding protein that interacts with the cyclic nucleotide-responsive sequence in the Type-1 plasminogen activator inhibitor mRNA. Heaton, J.H., Dlakic, W.M., Dlakic, M., Gelehrter, T.D. J. Biol. Chem. (2001) [Pubmed]
  13. Cloning and intracellular localization of the U2 small nuclear ribonucleoprotein auxiliary factor small subunit. Zhang, M., Zamore, P.D., Carmo-Fonseca, M., Lamond, A.I., Green, M.R. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  14. The role of U2AF35 and U2AF65 in enhancer-dependent splicing. Graveley, B.R., Hertel, K.J., Maniatis, T. RNA (2001) [Pubmed]
  15. Intron removal requires proofreading of U2AF/3' splice site recognition by DEK. Soares, L.M., Zanier, K., Mackereth, C., Sattler, M., Valcárcel, J. Science (2006) [Pubmed]
  16. Functional association of nuclear protein 4.1 with pre-mRNA splicing factors. Lallena, M.J., Martínez, C., Valcárcel, J., Correas, I. J. Cell. Sci. (1998) [Pubmed]
  17. A radiation hybrid map of the RN region in pigs demonstrates conserved gene order compared with the human and mouse genomes. Robic, A., Seroude, V., Jeon, J.T., Yerle, M., Wasungu, L., Andersson, L., Gellin, J., Milan, D. Mamm. Genome (1999) [Pubmed]
WikiGenes - Universities