Post-Transcriptional Regulation of Gene Expression

Transcription and translation are spatially separated events in eucaryotes. The product of nuclear transcription is pre-mRNA. In order to enable translation, the information contained within the pre-mRNA must be transported out of the nucleus and into the cytosol. The quantity of processed mRNA available for translation decides to a high degree how much protein is formed by de novo synthesis. 

From the primary transcript to translated protein there are many possible points for regulatory processes. The most important regulatory points are  

The transport from nucleus to cytoplasm is accompanied by modification at the 5 - and 3 -end of the pre-RNA, as well as by processing (splicing) of the primary transcript. The 3 -end modifications and sphcing decide which information contained in the primary transcript is made available for protein biosynthesis. The information content of the processed mRNA can be specifically influenced by these processes. This has an important impact on the tissue- and cell-specific protein expression. 3 -modification and splicing are tightly coupled to extranuclear transport. Interventions in the transport process are another possibihty for a regulation at the post-transcriptional level. 

The translation of the correctly modified mature mRNA by the ribosome is also subject to regulation. The regulatory site of translation is mainly at the initiation of translation. Further regulatory elements include the availability of mRNA for ribosomal protein biosynthesis, as well as the concentration of mRNA. The availabihty of mRNA can be controlled by, for example, sequence-specific protein binding to the mRNA. The concentration of a specific mRNA is determined by a balance between its rate of synthesis (i.e. transcription) and its rate of degradation by RNases. The stabihty of a mRNA against nucleolytic degradation is thus a further factor that can determine the extent of biosynthesis of a protein. 

3 and 5 modifications and splicing are tightly coupled to transcription by RNA polymerase II. Interventions in these processes are another possibility for regulation at a level that is distinct from transcription per se. The intimate connection between transcription and pre-mRNA processing has been recognized only in recent years, when it became clear that components of the mRMA-modification systems are associated with the Carboy-terminal domain (CTD) of elongating RNA polymerase II. 

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Specific interactions between RNA and proteins are fundamental to many cellular processes, including the assembly and function of ribonucleoprotein particles (RNPs) and the post-transcriptional regulation of gene expression. Nearly all of the functions discovered for RNA involve binding of proteins (Haynes, 1999). Several proteins use a P-sheet surface to bind RNA and others insert an a-helix into the widened groove of a non-canonical RNA hehx. Distortion or rearrangement of the RNA structure by bound protein is a common feature of their interactions. 

Kuhlemeier, C. (1992) Transcriptional and post-transcriptional regulation of gene expression in plants. Plant Mol. Biol. 19, 1-14. 

Paulding WR, Czyzyk-Krzeska MR Post-transcriptional regulation of gene expression hy hypoxia. Adv Exp Med Biol 2000 475 111-122. 

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