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Section: Genetics » Regulation of Gene Expression » Mechanisms in Eukaryotes
 
 
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  Synthesis of mRNA in pieces in VSG genes in trypanosome
 
     
 
Content
⇒ Regulation of Gene Expression 3. A Variety of Mechanisms in Eukaryotes
⇒ Regulation at Transcription Level
⇒ Activation of transcription
⇒ Britten-Davidson model for unit of transcription
⇒ Gene battery
⇒ Chromosomal proteins and gene expression
⇒ Repression of transcription 
⇒ Specific DNA sequences controlling transcription
⇒ Transgenic plants to study regulatory sequences
⇒ Modification of DNA sequences and their transcripts in gene expression
⇒ Alternative splicing of transcripts
⇒ Regulation at translation level
⇒ Activation and repression of translation
⇒ Masked mRNA in eggs of sea urchin and Xenopus
⇒ Regulation by gene re-arrangement
⇒ Expression of immunoglobulin genes
⇒ Yeast mating type switching
⇒ Trypanosome surface antigen (VSG) switching
⇒ Synthesis of mRNA in pieces in VSG genes in trypanosome
⇒ Regulation by reversible phosphorylation
⇒ Signal transduction and second messengers
⇒ Proteins and peptide hormones and gene expression
⇒ Steroid hormones and gene expression
⇒ Interferon stimulated gene expression (without a second messenger)
⇒ Cell surface receptors in cholesterol metabolism and drug production
⇒ Ubiquitin protein and regulation of heat shock genes
Synthesis of mRNA in pieces in VSG genes in trypanosome
It is well established that in eukaryotes, a precursor mRNA is first synthesized, and is processed to give rise to mRNA. In split genes also (Organization of Genetic Material 3.  Split Genes, Overlapping Genes and Pseudogenes), a pre-mRNA is first synthesized and intron regions are then excised to give rise to mRNA. However, in trypanosome (Trypanosoma brucei), it was shown that the mRNA for some glycoproteins synthesized by VSG gene.s, has a small segment at its 5' end which is synthesized as a discrete transcript separate from the remainder of mRNA. It was also shown that DNA encoding this 35-nucleotides leader RNA sequence (called 'mini exon') of all VSG mRNAs is separated by 30 kilobases from the DNA segment coding for the remaining mRNA. This 35-nucleotides sequence is common to all trypanosome mRNAs. No precursor giant mRNA, which could give rise to this mRNA by post-transcriptional splicing, could be observed. It was therefore, concluded that 35-nucleotides 'mini exon' RNA was synthesized as a part of a separate transcript and then either (i) joined to the remainder of the m-RNA-through trans-splicing or (ii) acted as a primer for the transcription of the longer segment of mRNA.

It has also been shown that mRNA can be produced from two precursor molecules through trans-splicing followed by joining. This became possible through the availability of a technique for in vitro splicing systems. In a study from Massachusetts Institute of Technology, USA, two artificial mRNA precursors could be synthesized, one having LI exon and the other having L2 exon. These two exons could be spliced together under optimum in vitro conditions to enable them to join together. In another study from Yale University, USA, chimeric precursors had either (i) the exon adE1 and glE2 or (ii) the exons adE2 and glE1. In each of these chimeric precursors, the two exons were connected by an intron and it was shown that splicing may be (i) cis leading to production of mRNA having exons from the same precursor or may be (ii) trans leading to the production of mRNA having exons from two precursors. The former is an intramolecular reaction and the latter is an intermolecular reaction and both were shown to proceed at the same rate.

In the above experiments, it was shown that the introns of two precursors have complementary sequences and, therefore, can be brought together either by base pairing or by mutual binding of a polypeptide. A scheme of cis and trans splicing of two chimeric precursor mRNAs to give rise to one mRNA is shown in Figure 37.20.
 
Production of mRNA through splicing and rejoining of segments from different precursor mRNA molecules. (For details, see text).
Fig. 37.20. Production of mRNA through splicing and rejoining of segments from different precursor mRNA molecules. (For details, see text).

 
     






     
     
 
 
     
 
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