Regulation via Transport and Splicing of pre-mRNA

Splicing and transport of the transcript from the nucleus to the cytosol are tightly coupled. Unspliced pre-mRNA usually does not leave the nucleus, so that only correctly spliced mRNA reaches the cytosol. The hmnan immrmodeficiency virus (HIV) is an example of how manipulation of the nucleocytoplasmic transport can be used to create different mRNAs from one pre-mRNA (Cullen and Mahm, 1991). 

Following integration into the host genome as a provirus, the genome of a retrovirus is similar in many respects to a typical eucaryotic cellular gene. The transcription of the HIV coding DNA, modification and processing of the HIV transcript is performed by 

A key element of regulation is the Rev protein. In the absence of the Rev protein, one finds a multiply spliced class of 2S RNA in the cytoplasm that encodes the regulatory proteins Tat, Rev and Nef At this phase the mRNAs which encode structural protein are transported to the cytosol only at a low level. They are furthermore unstable and are only partially loaded with polysomes. 

In the presence of the Rev protein, however, mainly longer, unspliced 9S mRNAs and partially spliced viral RNAs are foimd in the cytosol, from which the expression of the structural proteins occurs. Normally incompletely spliced or imspliced mRNAs are retained in the nucleus and can not be transported to the cytosol. 

At the beginning of the replication cycle of HIV, before the Rev protein is present, primarily regulatory proteins are formed. If, in the framework of this expression pattern, enough Rev protein is present, then imspliced or incompletely spliced viral mRNAs appear in e cytosol and structural proteins are formed. 

RN As arise by differential splicing (Fig. 1.43). The remarkable thing about the splicing of HIV RNA is the fact that the splicing and hence transport of the pre-mRNA is regulated by a viral protein. 

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