6e5u

Structural highlights

Function

[I7CAR2_9INFA] Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage and polyadenylation specificity factor/CPSF4 and the poly(A)-binding protein 2/PABPN1. In turn, unprocessed 3' end pre-mRNAs accumulate in the host nucleus and are no longer exported to the cytoplasm. Cellular protein synthesis is thereby shut off very early after virus infection. Viral protein synthesis is not affected by the inhibition of the cellular 3' end processing machinery because the poly(A) tails of viral mRNAs are produced by the viral polymerase through a stuttering mechanism.[RuleBase:RU362113][SAAS:SAAS01036581] Prevents the establishment of the cellular antiviral state by inhibiting TRIM25-mediated DDX58 ubiquitination, which normally triggers the antiviral transduction signal that leads to the activation of type I IFN genes by transcription factors IRF3 and IRF7. Prevents human EIF2AK2/PKR activation, either by binding double-strand RNA, or by interacting directly with EIF2AK2/PKR. This function may be important at the very beginning of the infection, when NS1 is mainly present in the cytoplasm. Also binds poly(A) and U6 snRNA.[RuleBase:RU362113][SAAS:SAAS01036591] [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]}

References

1. ↑ 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
2. ↑ 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
3. ↑ 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
4. ↑ 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
5. ↑ 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
6. ↑ 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