Biology:ALYREF

Generic protein structure example

Aly/REF export factor, also known as THO complex subunit 4 is a protein that in humans is encoded by the ALYREF gene.

The ALYREF gene encodes Aly/REF export factor (ALY; THO complex subunit 4, Tho4; RNA and export factor binding protein 1, Refbp1), a ubiquitously expressed nuclear protein that functions as a molecular chaperone and export adapter involved in nuclear export of spliced and unspliced mRNA. The TRanscription-EXport (TREX) complex, a key player in mRNA export, includes the THO subcomplex, the RNA helicase UAP56, and the RNA-binding protein ALY. In yeast, TREX is recruited co-transcriptionally; in human cells it is recruited during a late step of splicing. The human TREX complex is recruited to a region near the 5' end of mRNA by interaction of ALY and THO with the nuclear cap-binding complex. As a chaperone, ALY promotes dimerization of transcription factors containing basic leucine zipper (bZIP) domains., thereby promoting transcriptional activation. ALY has key roles in 3'-end processing of polyadenylated mRNAs and in nuclear export of both polyadenylated and non-polyadenylated mRNAs. After mRNA binds to ALY, it is apparently transferred to the NXF1-NXT1 heterodimer for export (TAP/NFX1 pathway). The full-length ALY protein (Refbp1-I, 255 amino acids encoded by six exons) has a conserved RNA recognition motif (RRM; amino acids 105-182) flanked by alanine/arginine/glycine-rich sequences; an N-terminal region (amino acids 16-37) is sufficient for RNA binding and interaction with the NXF1-NXT1 heterodimer.

Further reading

• "ALY, a context-dependent coactivator of LEF-1 and AML-1, is required for TCRalpha enhancer function.". Genes Dev. 11 (5): 640–53. 1997. doi:10.1101/gad.11.5.640. PMID 9119228. 
• "Mass spectrometry and EST-database searching allows characterization of the multi-protein spliceosome complex.". Nat. Genet. 20 (1): 46–50. 1998. doi:10.1038/1700. PMID 9731529. 
• "Autoantibodies to transcriptional regulation proteins DEK and ALY in a patient with systemic lupus erythematosus.". Hum. Immunol. 60 (1): 57–62. 1999. doi:10.1016/S0198-8859(98)00085-8. PMID 9952027. 
• "A human nuclear-localized chaperone that regulates dimerization, DNA binding, and transcriptional activity of bZIP proteins.". Mol. Cell 4 (2): 219–28. 1999. doi:10.1016/S1097-2765(00)80369-X. PMID 10488337. 
• "The spliceosome deposits multiple proteins 20-24 nucleotides upstream of mRNA exon-exon junctions.". EMBO J. 19 (24): 6860–9. 2001. doi:10.1093/emboj/19.24.6860. PMID 11118221. 
• "Role of the nonsense-mediated decay factor hUpf3 in the splicing-dependent exon-exon junction complex.". Science 293 (5536): 1832–6. 2001. doi:10.1126/science.1062829. PMID 11546873. Bibcode: 2001Sci...293.1832K. 
• "Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly.". Nature 413 (6856): 644–7. 2001. doi:10.1038/35098106. PMID 11675789. Bibcode: 2001Natur.413..644L. 
• "Magoh, a human homolog of Drosophila mago nashi protein, is a component of the splicing-dependent exon-exon junction complex.". EMBO J. 20 (22): 6424–33. 2002. doi:10.1093/emboj/20.22.6424. PMID 11707413. 
• "TREX is a conserved complex coupling transcription with messenger RNA export.". Nature 417 (6886): 304–8. 2002. doi:10.1038/nature746. PMID 11979277. Bibcode: 2002Natur.417..304S. 
• "Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis.". RNA 8 (4): 426–39. 2002. doi:10.1017/S1355838202021088. PMID 11991638. 
• "Large-scale proteomic analysis of the human spliceosome.". Genome Res. 12 (8): 1231–45. 2002. doi:10.1101/gr.473902. PMID 12176931. 
• "ICP27 interacts with the RNA export factor Aly/REF to direct herpes simplex virus type 1 intronless mRNAs to the TAP export pathway.". J. Virol. 76 (24): 12877–89. 2002. doi:10.1128/JVI.76.24.12877-12889.2002. PMID 12438613. 
• "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M. 
• "An evolutionarily conserved role for SRm160 in 3'-end processing that functions independently of exon junction complex formation.". J. Biol. Chem. 278 (45): 44153–60. 2004. doi:10.1074/jbc.M306856200. PMID 12944400. 
• "Growth-regulated expression and G0-specific turnover of the mRNA that encodes URH49, a mammalian DExH/D box protein that is highly related to the mRNA export protein UAP56.". Nucleic Acids Res. 32 (6): 1857–65. 2004. doi:10.1093/nar/gkh347. PMID 15047853. 
• "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. 2004. doi:10.1101/gr.2596504. PMID 15489334. 
• "Identifying and quantifying in vivo methylation sites by heavy methyl SILAC.". Nat. Methods 1 (2): 119–26. 2005. doi:10.1038/nmeth715. PMID 15782174. 
• "Recruitment of the human TREX complex to mRNA during splicing.". Genes Dev. 19 (13): 1512–7. 2005. doi:10.1101/gad.1302205. PMID 15998806. 
• "ALY is a common coactivator of RUNX1 and c-Myb on the type B leukemogenic virus enhancer.". J. Virol. 81 (7): 3503–13. 2007. doi:10.1128/JVI.02253-06. PMID 17229714. 
• "Regulation of mRNA export by the PI3 kinase/AKT signal transduction pathway.". Mol. Biol. Cell 24 (8): 1208–21. 2013. doi:10.1091/mbc.E12-06-0450. PMID 23427269. 

External links

• ALYREF human gene location in the UCSC Genome Browser.
• ALYREF human gene details in the UCSC Genome Browser.
• Overview of all the structural information available in the PDB for UniProt: Q86V81 (THO complex subunit 4) at the PDBe-KB.