Nuclear export

Expoitins are transport receptors at the nuclear pore complex needed for the selective export of proteins from the nucleus into the cytoplasm. They recognize nuclear export signal sequences of cargo proteins. 

The NHR contains also the conserved Calcineurin docking site, PxlxIT, required for the physical interaction of NEAT and Calcineurin. Dephosphorylation of at least 13 serines residues in the NHR induces a conformational change that exposes the nuclear localization sequences (NLS), allowing the nuclear translocation of NEAT. Rephosphorylation of these residues unmasks the nuclear export sequences that direct transport back to the cytoplasm. Engagement of receptors such as the antigen receptors in T and B cells is coupled to phospholipase C activation and subsequent production of inositol triphosphate. Increased levels of inositol triphosphate lead to the initial release of intracellular stores of calcium. This early increase of calcium induces opening of the plasma membrane calcium-released-activated-calcium (CRAC) channels,... 

Nuclear export of unspliced RNA RevMlO Transdominant HIV Rev protein Dominant negative Sam68, a Rev homolog scFv to Rev RRE decoy HIV-1 Habu et al. 2005 Hotchkiss et al. 2004 Li et al. 1998a, b Yamada et al. 1994... 

Proteins similar to importins, referred to as ex-portins, are involved in export of many macromolecules from the nucleus. Cargo molecules for export carry nuclear export signals (NESs). Ran proteins are involved in this process also, and it is now established that the processes of import and export share a number of common feamres. 

The viral protein Rev may also play a role in HIV-1 latency. Expression of the viral Rev protein is essential for the nuclear export of genomic RNA as well as unspliced and/or singly spliced transcripts (Cullen 2003), which are ultimately translated into structural, regulatory, and enzymatic viral proteins. Retention of Rev and Tat (viral transactivator proteins) transcripts in the nucleus of resting CD4h- T cells from HAART patients (Lassen et al. 2006) might be involved in the maintenance of post-integration latency in these cells. Importantly, this phenomenon is non-existent in activated T cells. 

Sarkar, S., and Hopper, A. K. (1998). tRNA nuclear export in Saccharomyces cerevisiae In situ hybridization analysis. Mol. Biol. Cell 9, 3041-3055. 

Izaurralde, E., Stepinski, J., Darzynkiewicz, E., and Mattaj, I. W. (1992). A cap binding protein that may mediate nuclear export of RNA polymerase II-transcribed RNAs. J. Cell Biol. 118, 1287-1295. 

The Xenopus transcription factor IIIA not only acts as an essential RNA polymerase transcription factor for the expression of the 5S rRNA gene, it also binds to the 5S rRNA to form a 7S ribonucleoprotein particle that stabilizes the RNA until it is required for ribosome assembly and facilitates nuclear export of the 5S rRNA. Indeed, it was originally shown to be the protein component associated with 5S rRNA in the 7S particle in Xenopus oocytes before it was recognized as a transcription factor. How, we may ask, can this protein not only recognize specific DNA sequences in the 5S rRNA gene upstream region, but also recognize different, but equally specific, sequences in 5S rRNA ... 

The nucleus is surrounded by the nuclear envelope, which takes on a lumenal structure connected to the endoplasmic reticulum. The transport of proteins into (and out of) the nucleus occurs through the nuclear pore complex (NPC), a large complex composed of more than 100 different proteins (Talcott and Moore, 1999). Because NPC forms an aqueous pore across the two membranes, small proteins less than 9 nm in diameter can pass through it simply by diffusion. However, most of the transports of both proteins and RNAs are mediated by an active transport mechanism. It is now clear that there is heavy traffic through the NPC in both directions. Proteins are not only imported into the nucleus but also actively exported from it as well. There are many reasons for nuclear export. One reason is to send some shuttle proteins back after their import another is for some viral proteins to export their replicated genomes outside the nucleus. 

The last three signals are used for nuclear export. 

Once integrated into the host chromosome, the assembly of new viral particles necessitates the prodnction of viral RNA transcripts and proteins. Initiation of viral transcription is also an RNA independent process where host transcription promoters and enhancer elements such as NF-kB bind to the 5 -LTR. The host transcriptional complex is then recrnited and transcription commences.Once transcription has been initiated, RNA and RNA-RNA interactions play a critical role in mediating the production of viral transcripts. The multiprotein transcription complex has a recognition factor for nonhost DNA and quickly releases from viral DNA, creating short, abortive transcripts. Processing and nuclear export of these transcripts leads to the translation of the HIV Tat protein, a small early-phase viral protein (Figure 10.4) that plays a key role in the ultimate formation of fnll-length viral RNA transcripts. 

Full-length viral RNA transcripts are processed by the host machinery prior to nuclear export however, if only processed viral RNA transcripts were exported from the nucleus, viral replication would halt. Both partially spliced and fully unspliced viral RNA transcripts must be exported from the nucleus to serve as open reading frames for proteins (Gag, Pol, and Env) that are essential for completing the viral life cycle (Figures 10.1 and 10.3). Additionally, each new viral particle must contain two copies of the fully unspliced viral RNA, which serves as the primary genome for progeny virions. 

Regarding the localization of the majority of proteasomes to the nuclear rim and nuclear envelope, it seems likely, that proteasomal degradation requires nuclear export or translocation processes, which directs nuclear proteins at least to the nuclear pore or to the inner surface of the nucleus. This implies that all components of the ubiquitination machinery have to be active inside the nucleus, v ich seems to be a prerequisite for the specific export process. It is also possible that nucleus-specific kinases or E2/E3 enzymes promote the triggering of nuclear proteins for rapid degradation. 

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