ALYREF
Aly/REF export factor, also known as THO complex subunit 4 is a protein that in humans is encoded by the ALYREF gene.[5][6]
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.,[7] 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.[8][9] 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[10]) 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.[11]
References
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000183684 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000025134 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Muravenko OV, Gizatullin RZ, Al-Amin AN, Protopopov AI, Kashuba VI, Zelenin AV, Zabarovsky ER (Jan 2001). "Human ALY/BEF gene Map position 17q25.3". Chromosome Res. 8 (6): 562. doi:10.1023/A:1009236126053. PMID 11032328. S2CID 6859937.
- ^ "Entrez Gene: ALYREF Aly/REF export factor".
- ^ "Entrez Gene: THOC4 THO complex 4".
- ^ Shi M, Zhang H, Wu X, He Z, Wang L, Yin S, Tian B, Li G, Cheng H (Sep 2017). "ALYREF mainly binds to the 5' and the 3' regions of the mRNA in vivo". Nucleic Acids Res. 45 (16): 9640–9653. doi:10.1093/nar/gkx597. PMC 5766156. PMID 28934468.
- ^ Shi M, Zhang H, Wu X, He Z, Wang L, Yin S, Tian B, Li G, Cheng H (Mar 2019). "ALYREF links 3'-end processing to nuclear export of non-polyadenylated mRNAs". EMBO J. 38 (9): e99910. doi:10.15252/embj.201899910. PMC 6484419. PMID 30858280.
- ^ "Ensembl: Gene ALYREF ENSG00000183684 (human)".
- ^ "UniProtKB Q86V81 (THOC4_HUMAN)".
Further reading
[edit]- Bruhn L, Munnerlyn A, Grosschedl R (1997). "ALY, a context-dependent coactivator of LEF-1 and AML-1, is required for TCRalpha enhancer function". Genes Dev. 11 (5): 640–53. doi:10.1101/gad.11.5.640. PMID 9119228.
- Neubauer G, King A, Rappsilber J, et al. (1998). "Mass spectrometry and EST-database searching allows characterization of the multi-protein spliceosome complex". Nat. Genet. 20 (1): 46–50. doi:10.1038/1700. PMID 9731529. S2CID 585778.
- Wichmann I, Garcia-Lozano JR, Respaldiza N, et al. (1999). "Autoantibodies to transcriptional regulation proteins DEK and ALY in a patient with systemic lupus erythematosus". Hum. Immunol. 60 (1): 57–62. doi:10.1016/S0198-8859(98)00085-8. PMID 9952027.
- Virbasius CM, Wagner S, Green MR (1999). "A human nuclear-localized chaperone that regulates dimerization, DNA binding, and transcriptional activity of bZIP proteins". Mol. Cell. 4 (2): 219–28. doi:10.1016/S1097-2765(00)80369-X. PMID 10488337.
- Le Hir H, Izaurralde E, Maquat LE, Moore MJ (2001). "The spliceosome deposits multiple proteins 20-24 nucleotides upstream of mRNA exon-exon junctions". EMBO J. 19 (24): 6860–9. doi:10.1093/emboj/19.24.6860. PMC 305905. PMID 11118221.
- Kim VN, Kataoka N, Dreyfuss G (2001). "Role of the nonsense-mediated decay factor hUpf3 in the splicing-dependent exon-exon junction complex". Science. 293 (5536): 1832–6. Bibcode:2001Sci...293.1832K. doi:10.1126/science.1062829. PMID 11546873. S2CID 12018200.
- Luo ML, Zhou Z, Magni K, et al. (2001). "Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly". Nature. 413 (6856): 644–7. Bibcode:2001Natur.413..644L. doi:10.1038/35098106. PMID 11675789. S2CID 4395388.
- Kataoka N, Diem MD, Kim VN, et al. (2002). "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. doi:10.1093/emboj/20.22.6424. PMC 125744. PMID 11707413.
- Strässer K, Masuda S, Mason P, et al. (2002). "TREX is a conserved complex coupling transcription with messenger RNA export". Nature. 417 (6886): 304–8. Bibcode:2002Natur.417..304S. doi:10.1038/nature746. PMID 11979277. S2CID 1112194.
- Jurica MS, Licklider LJ, Gygi SR, et al. (2002). "Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis". RNA. 8 (4): 426–39. doi:10.1017/S1355838202021088. PMC 1370266. PMID 11991638.
- Rappsilber J, Ryder U, Lamond AI, Mann M (2002). "Large-scale proteomic analysis of the human spliceosome". Genome Res. 12 (8): 1231–45. doi:10.1101/gr.473902. PMC 186633. PMID 12176931.
- Chen IH, Sciabica KS, Sandri-Goldin RM (2002). "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. doi:10.1128/JVI.76.24.12877-12889.2002. PMC 136725. PMID 12438613.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- McCracken S, Longman D, Johnstone IL, et al. (2004). "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. doi:10.1074/jbc.M306856200. PMID 12944400.
- Pryor A, Tung L, Yang Z, et al. (2004). "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. doi:10.1093/nar/gkh347. PMC 390356. PMID 15047853.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Ong SE, Mittler G, Mann M (2005). "Identifying and quantifying in vivo methylation sites by heavy methyl SILAC". Nat. Methods. 1 (2): 119–26. doi:10.1038/nmeth715. PMID 15782174. S2CID 6654604.
- Masuda S, Das R, Cheng H, et al. (2005). "Recruitment of the human TREX complex to mRNA during splicing". Genes Dev. 19 (13): 1512–7. doi:10.1101/gad.1302205. PMC 1172058. PMID 15998806.
- Mertz JA, Kobayashi R, Dudley JP (2007). "ALY is a common coactivator of RUNX1 and c-Myb on the type B leukemogenic virus enhancer". J. Virol. 81 (7): 3503–13. doi:10.1128/JVI.02253-06. PMC 1866045. PMID 17229714.
- Quaresma AJ, Sievert R, Nickerson JA (2013). "Regulation of mRNA export by the PI3 kinase/AKT signal transduction pathway". Mol. Biol. Cell. 24 (8): 1208–21. doi:10.1091/mbc.E12-06-0450. PMC 3623641. PMID 23427269.
External links
[edit]- 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.
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