Trypanosomes, trans- splicing

Watkins, K. P. and Agabian, N. (1991) In vivo UV cross-linking of U snRNAs that participate in trypanosome trans-splicing. Genes Dev. 5 1859 1869. 

Muhich, M.L. Boothroyd, J.C. (1989). Synthesis of trypanosome hsp70 mRNA is resistant to disruption of trans-splicing by heat shock Mol. Cell. Biol. 8, 3837-3846. 

Trans splicing. Every mRNA in trypanosomes has, at its 5 end, a short 35-nucleotide sequence that is not encoded in the transcribed gene. It was found that for each mRNA molecule two transcripts are formed and are spliced together, always with the 5 piece from a short SL (spliced leader) gene being joined to each of the others.639 This trans splicing has since been observed in many plants, animals, and protists.640... 

FIG. 1.1 Biogenesis of trypanosomatid mRNA. A schematic view of trypanosome gene expression. Mature mRNAs are generated from polycistronic pre-mRNAs via two RNA processing reactions, trans-splicing and polyadenylation. For details, see text. 

Polycistronic transcription units are typical of prokaryotic organisms and of some eukaryotic viruses. Trypanosomes (and nematodes which also trans-splice, see below) represent the only examples of eukaryotes which transcribe their genes in this way. At present, there is no evidence that the various genes encoded in polycistronic transcription units in trypanosomes are related in their function as are operons in bacteria. Likewise, we do not know what the average size of a transcription unit is in trypanosomatids and whether there is any attenuation of transcription in regions that are promoter-distal relative to those that are promoter-proximal. This latter consideration has obvious relevance for the control of gene expression in these organisms. 

The lack of SL RNA cap recognition in nematode trans-splicing stands in apparent contrast to recent results obtained in trypanosomes. Two groups have shown that trypanosome SL RNAs, undermethylated in the cap structure, do no function in trans-splicing. These results suggest that the unique trypanosome SL RNA cap may be required at some point in the assembly of the trans-spliceosome. However, this interpretation is not clear, since it is possible that, as with other snRNAs, the cap could serve to localize the trypanosome SL RNA to the nucleus. Until the pathway of SL RNP assembly is worked out or a trypanosome cell free system is established this will remain an open question. Nevertheless, the enzymes that catalyze cap modification in... 

As discussed above, trans-splicing serves to mature 5 ends of mRNAs embedded with polycistronic transcription units in trypanosomes and may serve the same function in nematodes. However, trans-splicing may be important in other aspects of mRNA metabolism. 

In addition to providing a discrete 5 end for mRNAs, trans-splicing also provides each mRNA with the cap structure derived from the SL RNA. Although it remains to be established whether translation in trypanosomes or nematodes is cap dependent, it seems likely that the cap, as it is in other eukaryotes, will be essential for mRNA recognition by ribosomes. It remains to be determined whether spliced leader or cap addition is necessary for transport of mRNAs from the nucleus or influences mRNA stability. 

Tschudi, C. and Ullu, E. (1990) Destruction of U2, U4 or U6 small nuclear RNAs blocks trans-splicing in trypanosome cells. Cell 61 459-466. 

Ullu, E., Matthews, K. R. and Tschudi, C. (1993) Temporal order of RNA process reactions in trypanosomes rapid trans-splicing precedes polyadenylation of newly-synthesized tubulin transcripts. Mol. Cell Biol. 13 720 725. 

Laird, P. (1989) Trans-splicing in trypanosomes — archaism or adaptation Trends Genet. 5 204-208. 

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