| Structural highlights
Function
[NXF1_HUMAN] Involved in the nuclear export of mRNA species bearing retroviral constitutive transport elements (CTE) and in the export of mRNA from the nucleus to the cytoplasm. The NXF1-NXT1 heterodimer is involved in the export of HSP70 mRNA in conjunction with ALYREF/THOC4 and THOC5.[1] [2] [NXT1_HUMAN] Stimulator of protein export for NES-containing proteins. Also plays a role in the nuclear export of U1 snRNA, tRNA, and mRNA. The NXF1-NXT1 heterodimer is involved in the export of HSP70 mRNA in conjunction with ALYREF/THOC4 and THOC5.[3] [4] [5] [6]
Publication Abstract from PubMed
The NXF1:NXT1 complex (also known as TAP:p15) is a general mRNA nuclear export factor that is conserved from yeast to humans. NXF1 is a modular protein constructed from four domains (RRM, LRR, NTF2-like and UBA domains). It is currently unclear how NXF1:NXT1 binds transcripts and whether there is higher organization of the NXF1 domains. We report here the 3.4 A resolution crystal structure of the first three domains of human NXF1 together with NXT1 that has two copies of the complex in the asymmetric unit arranged to form an intimate domain-swapped dimer. In this dimer, the linkers between the NXF1 LRR and NTF2-like domains interact with NXT1, generating a 2-fold symmetric platform in which the RNA-binding RRM, LRR and NTF2-like domains are arranged on one face. In addition to bulk transcripts, NXF1:NXT1 also facilitates the export of unspliced retroviral genomic RNA from simple type-D retroviruses such as SRV-1 that contain a constitutive transport element (CTE), a cis-acting 2-fold symmetric RNA stem-loop motif. Complementary structural, biochemical and cellular techniques indicated that the formation of a symmetric RNA binding platform generated by dimerization of NXF1:NXT1 facilitates the recognition of CTE-RNA and promotes its nuclear export.
The principal mRNA nuclear export factor NXF1:NXT1 forms a symmetric binding platform that facilitates export of retroviral CTE-RNA.,Aibara S, Katahira J, Valkov E, Stewart M Nucleic Acids Res. 2015 Jan 27. pii: gkv032. PMID:25628361[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gruter P, Tabernero C, von Kobbe C, Schmitt C, Saavedra C, Bachi A, Wilm M, Felber BK, Izaurralde E. TAP, the human homolog of Mex67p, mediates CTE-dependent RNA export from the nucleus. Mol Cell. 1998 Apr;1(5):649-59. PMID:9660949
- ↑ Katahira J, Inoue H, Hurt E, Yoneda Y. Adaptor Aly and co-adaptor Thoc5 function in the Tap-p15-mediated nuclear export of HSP70 mRNA. EMBO J. 2009 Mar 4;28(5):556-67. doi: 10.1038/emboj.2009.5. Epub 2009 Jan 22. PMID:19165146 doi:10.1038/emboj.2009.5
- ↑ Black BE, Levesque L, Holaska JM, Wood TC, Paschal BM. Identification of an NTF2-related factor that binds Ran-GTP and regulates nuclear protein export. Mol Cell Biol. 1999 Dec;19(12):8616-24. PMID:10567585
- ↑ Ossareh-Nazari B, Maison C, Black BE, Levesque L, Paschal BM, Dargemont C. RanGTP-binding protein NXT1 facilitates nuclear export of different classes of RNA in vitro. Mol Cell Biol. 2000 Jul;20(13):4562-71. PMID:10848583
- ↑ Guzik BW, Levesque L, Prasad S, Bor YC, Black BE, Paschal BM, Rekosh D, Hammarskjold ML. NXT1 (p15) is a crucial cellular cofactor in TAP-dependent export of intron-containing RNA in mammalian cells. Mol Cell Biol. 2001 Apr;21(7):2545-54. PMID:11259602 doi:10.1128/MCB.21.7.2545-2554.2001
- ↑ Katahira J, Inoue H, Hurt E, Yoneda Y. Adaptor Aly and co-adaptor Thoc5 function in the Tap-p15-mediated nuclear export of HSP70 mRNA. EMBO J. 2009 Mar 4;28(5):556-67. doi: 10.1038/emboj.2009.5. Epub 2009 Jan 22. PMID:19165146 doi:10.1038/emboj.2009.5
- ↑ Aibara S, Katahira J, Valkov E, Stewart M. The principal mRNA nuclear export factor NXF1:NXT1 forms a symmetric binding platform that facilitates export of retroviral CTE-RNA. Nucleic Acids Res. 2015 Jan 27. pii: gkv032. PMID:25628361 doi:http://dx.doi.org/10.1093/nar/gkv032
|
