Nxt1-KO Mouse

Nxt1, also known as p15 or p15-1, is an NTF2-like export protein. It shuttles between the nucleus and cytoplasm of metazoan cells and is crucial for the nuclear export of a diverse range of RNAs. It is involved in pathways like Crm1-dependent nuclear export, and the Nxf/Nxt (TAP/p15) RNA nuclear export pathway which is important for most mRNA nuclear export [1,2,5,6,7,8,9]. Genetic studies in primates and murine rodents suggest functional constraints on Nxt1, highlighting the value of these genetic models for its study [1].

In Drosophila, a partial loss-of-function allele of Nxt1 leads to reduced viability, sterility, and muscle degeneration. RNA-seq shows reduced expression of mRNAs, especially those from genes with long introns, and differential expression of circRNAs in Nxt1 mutants [4]. In mammalian cells, Nxt1 is a crucial cofactor in TAP-dependent export of intron-containing RNA. Its binding to TAP enhances RNA export, and formation of Tap/Nxt1 heterodimers activates Tap-dependent nuclear mRNA export by enhancing recruitment to nuclear pore complexes [6,8]. In influenza virus infection, Nxt1 promotes the nuclear export of nucleoprotein via a CRM1-dependent pathway, and Nxt1-knockdown cells exhibit decreased viral replication [3].

In conclusion, Nxt1 is essential for RNA nuclear export, playing key roles in processes like maintaining muscle integrity in Drosophila, tissue-specific transcriptional regulation, and viral replication in influenza. These findings from model-based research, especially the loss-of-function studies in Drosophila and functional studies in mammalian cells, help understand its biological functions and its potential as a target in antiviral drug development [3,4,5].

References:

1. Hu, Jia, Wang, Hong, He, Dan, Lyu, Yongqing, Li, Yan. 2022. Genetic characterization of nuclear export factor NXT1 and its paralog NXT2 in primates and murine rodents. In Zoology (Jena, Germany), 151, 126002. doi:10.1016/j.zool.2022.126002. https://pubmed.ncbi.nlm.nih.gov/35219094/

2. Black, B E, Holaska, J M, Lévesque, L, Dargemont, C, Paschal, B M. . NXT1 is necessary for the terminal step of Crm1-mediated nuclear export. In The Journal of cell biology, 152, 141-55. doi:. https://pubmed.ncbi.nlm.nih.gov/11149927/

3. Chutiwitoonchai, Nopporn, Aida, Yoko. 2016. NXT1, a Novel Influenza A NP Binding Protein, Promotes the Nuclear Export of NP via a CRM1-Dependent Pathway. In Viruses, 8, . doi:10.3390/v8080209. https://pubmed.ncbi.nlm.nih.gov/27483302/

4. van der Graaf, Kevin, Jindrich, Katia, Mitchell, Robert, White-Cooper, Helen. . Roles for RNA export factor, Nxt1, in ensuring muscle integrity and normal RNA expression in Drosophila. In G3 (Bethesda, Md.), 11, . doi:10.1093/g3journal/jkaa046. https://pubmed.ncbi.nlm.nih.gov/33561245/

5. Caporilli, Simona, Yu, Yachuan, Jiang, Jianqiao, White-Cooper, Helen. 2013. The RNA export factor, Nxt1, is required for tissue specific transcriptional regulation. In PLoS genetics, 9, e1003526. doi:10.1371/journal.pgen.1003526. https://pubmed.ncbi.nlm.nih.gov/23754955/

6. Guzik, B W, Levesque, L, Prasad, S, Rekosh, D, Hammarskjöld, M L. . NXT1 (p15) is a crucial cellular cofactor in TAP-dependent export of intron-containing RNA in mammalian cells. In Molecular and cellular biology, 21, 2545-54. doi:. https://pubmed.ncbi.nlm.nih.gov/11259602/

7. Aibara, Shintaro, Katahira, Jun, Valkov, Eugene, Stewart, Murray. 2015. The principal mRNA nuclear export factor NXF1:NXT1 forms a symmetric binding platform that facilitates export of retroviral CTE-RNA. In Nucleic acids research, 43, 1883-93. doi:10.1093/nar/gkv032. https://pubmed.ncbi.nlm.nih.gov/25628361/

8. Wiegand, Heather L, Coburn, Glen A, Zeng, Yan, Bogerd, Hal P, Cullen, Bryan R. . Formation of Tap/NXT1 heterodimers activates Tap-dependent nuclear mRNA export by enhancing recruitment to nuclear pore complexes. In Molecular and cellular biology, 22, 245-56. doi:. https://pubmed.ncbi.nlm.nih.gov/11739738/

9. Lévesque, L, Guzik, B, Guan, T, Hammarskjöld, M L, Paschal, B M. 2001. RNA export mediated by tap involves NXT1-dependent interactions with the nuclear pore complex. In The Journal of biological chemistry, 276, 44953-62. doi:. https://pubmed.ncbi.nlm.nih.gov/11579093/