| Structural highlights
Function
[UAP56_HUMAN] Component of the THO subcomplex of the TREX complex. The TREX complex specifically associates with spliced mRNA and not with unspliced pre-mRNA. It is recruited to spliced mRNAs by a transcription-independent mechanism. Binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export. The recruitment occurs via an interaction between ALYREF/THOC4 and the cap-binding protein NCBP1. DDX39B functions as a bridge between ALYREF/THOC4 and the THO complex. The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production. The recruitment of the TREX complex to the intronless viral mRNA occurs via an interaction between KSHV ORF57 protein and ALYREF/THOC4.[1] [2] [3] [4] [5] [6] [7] [8] Splice factor that is required for the first ATP-dependent step in spliceosome assembly and for the interaction of U2 snRNP with the branchpoint. Has both RNA-stimulated ATP binding/hydrolysis activity and ATP-dependent RNA unwinding activity. Even with the stimulation of RNA, the ATPase activity is weak. Can only hydrolyze ATP but not other NTPs. The RNA stimulation of ATPase activity does not have a strong preference for the sequence and length of the RNA. However, ssRNA stimulates the ATPase activity much more strongly than dsRNA. Can unwind 5' or 3' overhangs or blunt end RNA duplexes in vitro. The ATPase and helicase activities are not influenced by U2AF2 and ALYREF/THOC4.[9] [10] [11] [12] [13] [14] [15] [16]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Pre-mRNA splicing requires the function of a number of RNA-dependent ATPases/helicases, yet no three-dimensional structure of any spliceosomal ATPases/helicases is known. The highly conserved DECD-box protein UAP56/Sub2 is an essential splicing factor that is also important for mRNA export. The expected ATPase/helicase activity appears to be essential for the UAP56/Sub2 functions. Here, we show that purified human UAP56 is an active RNA-dependent ATPase, and we also report the crystal structures of UAP56 alone and in complex with ADP, as well as a DECD to DEAD mutant. The structures reveal a unique spatial arrangement of the two conserved helicase domains, and ADP-binding induces significant conformational changes of key residues in the ATP-binding pocket. Our structural analyses suggest a specific protein-RNA displacement model of UAP56/Sub2. The detailed structural information provides important mechanistic insights into the splicing function of UAP56/Sub2. The structures also will be useful for the analysis of other spliceosomal DExD-box ATPases/helicases.
Crystal structure of the human ATP-dependent splicing and export factor UAP56.,Shi H, Cordin O, Minder CM, Linder P, Xu RM Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17628-33. Epub 2004 Dec 7. PMID:15585580[17]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fleckner J, Zhang M, Valcarcel J, Green MR. U2AF65 recruits a novel human DEAD box protein required for the U2 snRNP-branchpoint interaction. Genes Dev. 1997 Jul 15;11(14):1864-72. PMID:9242493
- ↑ Luo ML, Zhou Z, Magni K, Christoforides C, Rappsilber J, Mann M, Reed R. Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly. Nature. 2001 Oct 11;413(6856):644-7. PMID:11675789 doi:http://dx.doi.org/10.1038/35098106
- ↑ Guo S, Hakimi MA, Baillat D, Chen X, Farber MJ, Klein-Szanto AJ, Cooch NS, Godwin AK, Shiekhattar R. Linking transcriptional elongation and messenger RNA export to metastatic breast cancers. Cancer Res. 2005 Apr 15;65(8):3011-6. PMID:15833825 doi:http://dx.doi.org/10.1158/0008-5472.CAN-04-3624
- ↑ Masuda S, Das R, Cheng H, Hurt E, Dorman N, Reed R. Recruitment of the human TREX complex to mRNA during splicing. Genes Dev. 2005 Jul 1;19(13):1512-7. PMID:15998806 doi:http://dx.doi.org/10.1101/gad.1302205
- ↑ Cheng H, Dufu K, Lee CS, Hsu JL, Dias A, Reed R. Human mRNA export machinery recruited to the 5' end of mRNA. Cell. 2006 Dec 29;127(7):1389-400. PMID:17190602 doi:http://dx.doi.org/10.1016/j.cell.2006.10.044
- ↑ Shen J, Zhang L, Zhao R. Biochemical characterization of the ATPase and helicase activity of UAP56, an essential pre-mRNA splicing and mRNA export factor. J Biol Chem. 2007 Aug 3;282(31):22544-50. Epub 2007 Jun 11. PMID:17562711 doi:http://dx.doi.org/10.1074/jbc.M702304200
- ↑ Boyne JR, Colgan KJ, Whitehouse A. Recruitment of the complete hTREX complex is required for Kaposi's sarcoma-associated herpesvirus intronless mRNA nuclear export and virus replication. PLoS Pathog. 2008 Oct;4(10):e1000194. doi: 10.1371/journal.ppat.1000194. Epub, 2008 Oct 31. PMID:18974867 doi:http://dx.doi.org/10.1371/journal.ppat.1000194
- ↑ Shi H, Cordin O, Minder CM, Linder P, Xu RM. Crystal structure of the human ATP-dependent splicing and export factor UAP56. Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17628-33. Epub 2004 Dec 7. PMID:15585580
- ↑ Fleckner J, Zhang M, Valcarcel J, Green MR. U2AF65 recruits a novel human DEAD box protein required for the U2 snRNP-branchpoint interaction. Genes Dev. 1997 Jul 15;11(14):1864-72. PMID:9242493
- ↑ Luo ML, Zhou Z, Magni K, Christoforides C, Rappsilber J, Mann M, Reed R. Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly. Nature. 2001 Oct 11;413(6856):644-7. PMID:11675789 doi:http://dx.doi.org/10.1038/35098106
- ↑ Guo S, Hakimi MA, Baillat D, Chen X, Farber MJ, Klein-Szanto AJ, Cooch NS, Godwin AK, Shiekhattar R. Linking transcriptional elongation and messenger RNA export to metastatic breast cancers. Cancer Res. 2005 Apr 15;65(8):3011-6. PMID:15833825 doi:http://dx.doi.org/10.1158/0008-5472.CAN-04-3624
- ↑ Masuda S, Das R, Cheng H, Hurt E, Dorman N, Reed R. Recruitment of the human TREX complex to mRNA during splicing. Genes Dev. 2005 Jul 1;19(13):1512-7. PMID:15998806 doi:http://dx.doi.org/10.1101/gad.1302205
- ↑ Cheng H, Dufu K, Lee CS, Hsu JL, Dias A, Reed R. Human mRNA export machinery recruited to the 5' end of mRNA. Cell. 2006 Dec 29;127(7):1389-400. PMID:17190602 doi:http://dx.doi.org/10.1016/j.cell.2006.10.044
- ↑ Shen J, Zhang L, Zhao R. Biochemical characterization of the ATPase and helicase activity of UAP56, an essential pre-mRNA splicing and mRNA export factor. J Biol Chem. 2007 Aug 3;282(31):22544-50. Epub 2007 Jun 11. PMID:17562711 doi:http://dx.doi.org/10.1074/jbc.M702304200
- ↑ Boyne JR, Colgan KJ, Whitehouse A. Recruitment of the complete hTREX complex is required for Kaposi's sarcoma-associated herpesvirus intronless mRNA nuclear export and virus replication. PLoS Pathog. 2008 Oct;4(10):e1000194. doi: 10.1371/journal.ppat.1000194. Epub, 2008 Oct 31. PMID:18974867 doi:http://dx.doi.org/10.1371/journal.ppat.1000194
- ↑ Shi H, Cordin O, Minder CM, Linder P, Xu RM. Crystal structure of the human ATP-dependent splicing and export factor UAP56. Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17628-33. Epub 2004 Dec 7. PMID:15585580
- ↑ Shi H, Cordin O, Minder CM, Linder P, Xu RM. Crystal structure of the human ATP-dependent splicing and export factor UAP56. Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17628-33. Epub 2004 Dec 7. PMID:15585580
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