ALYREF explained

Aly/REF export factor, also known as THO complex subunit 4 is a protein that in humans is encoded by the ALYREF gene.^{[1] [2]}

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.,^[3] 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.^{[4] [5]} 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^[6]) 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.^[7]

Further reading

• Bruhn L, Munnerlyn A, Grosschedl R . ALY, a context-dependent coactivator of LEF-1 and AML-1, is required for TCRalpha enhancer function. . Genes Dev. . 11 . 5 . 640–53 . 1997 . 9119228 . 10.1101/gad.11.5.640 . free .
• Neubauer G, King A, Rappsilber J . Mass spectrometry and EST-database searching allows characterization of the multi-protein spliceosome complex. . Nat. Genet. . 20 . 1 . 46–50 . 1998 . 9731529 . 10.1038/1700 . 585778 . etal.
• Wichmann I, Garcia-Lozano JR, Respaldiza N . Autoantibodies to transcriptional regulation proteins DEK and ALY in a patient with systemic lupus erythematosus. . Hum. Immunol. . 60 . 1 . 57–62 . 1999 . 9952027 . 10.1016/S0198-8859(98)00085-8 . etal.
• Virbasius CM, Wagner S, Green MR . A human nuclear-localized chaperone that regulates dimerization, DNA binding, and transcriptional activity of bZIP proteins. . Mol. Cell . 4 . 2 . 219–28 . 1999 . 10488337 . 10.1016/S1097-2765(00)80369-X . free .
• Le Hir H, Izaurralde E, Maquat LE, Moore MJ . The spliceosome deposits multiple proteins 20-24 nucleotides upstream of mRNA exon-exon junctions. . EMBO J. . 19 . 24 . 6860–9 . 2001 . 11118221 . 10.1093/emboj/19.24.6860 . 305905 .
• Kim VN, Kataoka N, Dreyfuss G . Role of the nonsense-mediated decay factor hUpf3 in the splicing-dependent exon-exon junction complex. . Science . 293 . 5536 . 1832–6 . 2001 . 11546873 . 10.1126/science.1062829 . 2001Sci...293.1832K . 12018200 .
• Luo ML, Zhou Z, Magni K . Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly. . Nature . 413 . 6856 . 644–7 . 2001 . 11675789 . 10.1038/35098106 . 2001Natur.413..644L . 4395388 . etal.
• Kataoka N, Diem MD, Kim VN . 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 . 11707413 . 10.1093/emboj/20.22.6424 . 125744 . etal.
• Strässer K, Masuda S, Mason P . TREX is a conserved complex coupling transcription with messenger RNA export. . Nature . 417 . 6886 . 304–8 . 2002 . 11979277 . 10.1038/nature746 . 2002Natur.417..304S . 1112194 . etal.
• Jurica MS, Licklider LJ, Gygi SR . Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis. . RNA . 8 . 4 . 426–39 . 2002 . 11991638 . 10.1017/S1355838202021088 . 1370266 . etal.
• Rappsilber J, Ryder U, Lamond AI, Mann M . Large-scale proteomic analysis of the human spliceosome. . Genome Res. . 12 . 8 . 1231–45 . 2002 . 12176931 . 10.1101/gr.473902 . 186633 .
• Chen IH, Sciabica KS, Sandri-Goldin RM . 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 . 12438613 . 10.1128/JVI.76.24.12877-12889.2002 . 136725 .
• Strausberg RL, Feingold EA, Grouse LH . 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 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• McCracken S, Longman D, Johnstone IL . 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 . 12944400 . 10.1074/jbc.M306856200 . etal. free .
• Pryor A, Tung L, Yang Z . 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 . 15047853 . 10.1093/nar/gkh347 . 390356 . etal.
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Ong SE, Mittler G, Mann M . Identifying and quantifying in vivo methylation sites by heavy methyl SILAC. . Nat. Methods . 1 . 2 . 119–26 . 2005 . 15782174 . 10.1038/nmeth715 . 6654604 .
• Masuda S, Das R, Cheng H . Recruitment of the human TREX complex to mRNA during splicing. . Genes Dev. . 19 . 13 . 1512–7 . 2005 . 15998806 . 10.1101/gad.1302205 . 1172058 . etal.
• Mertz JA, Kobayashi R, Dudley JP . ALY is a common coactivator of RUNX1 and c-Myb on the type B leukemogenic virus enhancer. . J. Virol. . 81 . 7 . 3503–13 . 2007 . 17229714 . 10.1128/JVI.02253-06 . 1866045 .
• Quaresma AJ, Sievert R, Nickerson JA . Regulation of mRNA export by the PI3 kinase/AKT signal transduction pathway. . Mol. Biol. Cell . 24. 8 . 1208–21 . 2013 . 23427269 . 10.1091/mbc.E12-06-0450 . 3623641 .

Notes and References

1. Muravenko OV, Gizatullin RZ, Al-Amin AN, Protopopov AI, Kashuba VI, Zelenin AV, Zabarovsky ER . Human ALY/BEF gene Map position 17q25.3 . Chromosome Res . 8 . 6 . 562 . Jan 2001 . 11032328 . 10.1023/A:1009236126053 . 6859937 .
2. Web site: Entrez Gene: ALYREF Aly/REF export factor.
3. Web site: Entrez Gene: THOC4 THO complex 4.
4. Shi M, Zhang H, Wu X, He Z, Wang L, Yin S, Tian B, Li G, Cheng H . ALYREF mainly binds to the 5' and the 3' regions of the mRNA in vivo. . Nucleic Acids Res . 45 . 16 . 9640–9653 . Sep 2017 . 28934468 . 5766156 . 10.1093/nar/gkx597 .
5. Shi M, Zhang H, Wu X, He Z, Wang L, Yin S, Tian B, Li G, Cheng H . ALYREF links 3'-end processing to nuclear export of non-polyadenylated mRNAs. . EMBO J . 38 . 9 . e99910 . Mar 2019 . 30858280 . 6484419. 10.15252/embj.201899910 .
6. Web site: Ensembl: Gene ALYREF ENSG00000183684 (human).
7. Web site: UniProtKB Q86V81 (THOC4_HUMAN).