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RNA Metabolism in Trypanosomes: Approaches to Unravel pre-mRNA Signals Required for Intron Removal

  • Christian Tschudi
  • Elisabetta Ullu
Chapter

Abstract

The study of RNA metabolism in trypanosomes has provided the scientific community with a number of unexpected and enticing discoveries, including polycistronic transcription (Ullu et al., 1996), trans-splicing (Ullu et al., 1996), cap 4 modification (Bangs et al., 1992), mitochondrial RNA editing (Hajduk et al., 1997; Simpson and Emeson, 1996; Stuart et al., 1997), coupling of trans-splicing and polyadenylation (Matthews et al., 1994), and more recently RNA interference or RNAi (Ngo et al., 1998). Furthermore, over the past few years we have learned that there is very little, if any, regulation of gene expression at the transcriptional level and that most likely modulation of gene expression is achieved primarily at the post-transcriptional level. In this scenario, the pre-mRNA cis-acting signals for RNA processing, by virtue of their interactions with processing machineries, would be major determinants for regulating gene expression.

Keywords

Polymerase Chain Reaction Splice Site Polymerase Chain Reaction Reaction Polymerase Chain Reaction Fragment Trypanosoma Brucei 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Ares, M., Jr., and Weiser, B. (1995). Rearrangement of snRNA structure during assembly and function of the spliceosome. Prog. Nucleic Acid. Res. Mol. Biol. 50, 131–159.PubMedCrossRefGoogle Scholar
  2. Bangs, J. D., Crain, P. F., Hashizume, T., McCloskey, J. A., and Boothroyd, J. C. (1992). Mass spectrometry of mRNA cap 4 from trypanosomatids reveals two novel nucleosides. J. Biol. Chem. 267, 9805–9815.PubMedGoogle Scholar
  3. Boothroyd, J. C., and Cross, G. A. (1982). Transcripts coding for variant surface glycoproteins of Tiypanosoma brucei have a short, identical exon at their 5’ end. Gene 20, 281–289.PubMedCrossRefGoogle Scholar
  4. Fantoni, A., Dare, A. O., and Tschudi, C. (1994). RNA polymerase III-mediated transcription of the trypanosome U2 small nuclear RNA gene is controlled by both intragenic and extragenic regulatory elements. Mol. Cell. Biol. 14, 2021–2028.PubMedGoogle Scholar
  5. Hajduk, S. L., Adler, B., Madison-Antenucci, S., McManus, M., and Sabatini, R. (1997). Insertional and deletional RNA editing in trypanosome mitochondria. Nucleic Acids Symp. Ser., 15–18.Google Scholar
  6. Hertel, K. J., Lynch, K. W., and Maniatis, T. (1997). Common themes in the function of transcription and splicing enhancers. Curr. Opin. Cell. Biol. 9, 350–357.PubMedCrossRefGoogle Scholar
  7. Krause, M., and Hirsh, D. (1987). A trans-spliced leader sequence on actin mRNA in C. elegans. Cell 49, 753–761.PubMedCrossRefGoogle Scholar
  8. Kunkel, T. A. (1985). Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc. Natl. Acad. Sci. U S A 82, 488–492.PubMedCrossRefGoogle Scholar
  9. Lopez-Estrano, C., Tschudi, C., and Ullu, E. (1998). Exonic sequences in the 5’ untranslated region of alpha-tubulin mRNA modulate trans splicing in Trypanosoma brucei. Mol. Cell. Biol. 18, 4620–4628.PubMedGoogle Scholar
  10. Mair, G., Shi, H., Li, H., Djikeng, A., Aviles, H.O., Bishop, J.R., Falcone, F.H., Gavrilescu, C., Montgomery, J.L., Santori, M.S., Stern, L.S., Wang., Z., Ullu, E. and Tschudi, C. (2000). A new twist in trypanosome RNA metabolism: cis-splicing of pre-mRNA. RNA, in press.Google Scholar
  11. Matthews, K. R., Tschudi, C., and Ullu, E. (1994). A common pyrimidine-rich motif governs trans-splicing and polyadenylation of tubulin polycistronic pre-mRNA in trypanosomes. Genes Dev. 8, 491–501.PubMedCrossRefGoogle Scholar
  12. Nakaar, V., Dare, A. O., Hong, D., Ullu, E., and Tschudi, C. (1994). Upstream tRNA genes are essential for expression of small nuclear and cytoplasmic RNA genes in trypanosomes. Mol. Cell. Biol. 14, 6736–6742.PubMedGoogle Scholar
  13. Ngo, H., Tschudi, C., Gull, K., and Ullu, E. (1998). Double-stranded RNA induces mRNA degradation in Trypanosoma brucei. Proc. Natl. Acad. Sci. U S A 95, 14687–14692.PubMedCrossRefGoogle Scholar
  14. Nilsen, T. W. (1994). RNA-RNA interactions in the spliceosome: unraveling the ties that bind. Cell 78, 1–4.PubMedCrossRefGoogle Scholar
  15. Rajkovic, A., Davis, R. E., Simonsen, J. N., and Rottman, F. M. (1990). A spliced leader is present on a subset of mRNAs from the human parasite Schistosoma mansoni. Proc. Natl. Acad. Sci. U S A 87, 8879–8883.PubMedCrossRefGoogle Scholar
  16. Reed, R. (1996). Initial splice-site recognition and pairing during pre-mRNA splicing. Curr. Opin. Genet. Dev. 6, 215–220.PubMedCrossRefGoogle Scholar
  17. Schnare, M. N., and Gray, M. W. (1999). A candidate Ul small nuclear RNA for trypanosomatid protozoa. J. Biol. Chem. 274, 23691–23694.PubMedCrossRefGoogle Scholar
  18. Simpson, L., and Emeson, R. B. (1996). RNA editing. Annu Rev Neurosci 19, 27–52.Google Scholar
  19. Stuart, K., Allen, T. E., Heidmann, S., and Seiwert, S. D. (1997). RNA editing in kinetoplastid protozoa. Microbiol. Mol. Biol. Rev. 61, 105–120.PubMedGoogle Scholar
  20. Tessier, L. H., Keller, M., Chan, R. L., Fournier, R., Weil, J. H., and Imbault, P. (1991). Short leader sequences may be transferred from small RNAs to pre-mature mRNAs by trans-splicing in Euglena. EMBO J. 10, 2621–2625.PubMedGoogle Scholar
  21. Ullu, E., Tschudi, C., and Gunzl, A. (1996). Trans-splicing in trypanosomatid protozoa. In Molecular biology of parasitic protozoa, D. F. Smith and M. Parsons, eds. ( Oxford, United Kingdom: Oxford University Press ), pp. 115–133.Google Scholar
  22. Wirtz, E., Leal, S., Ochatt, C., and Cross, G. A. (1999). A tightly regulated inducible expression system for conditional gene knock-outs and dominant-negative genetics in Trypanosoma brucei. Mol. Biochem. Parasitol. 99, 89–101.PubMedCrossRefGoogle Scholar
  23. Zahler, A. M., Lane, W. S., Stolk, J. A., and Roth, M. B. (1992). SR proteins: a conserved family of pre-mRNA splicing factors. Genes Dev. 6, 837–847.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2000

Authors and Affiliations

  • Christian Tschudi
    • 1
  • Elisabetta Ullu
    • 1
  1. 1.Department of Internal MedicineYale University School of MedicineNew HavenUSA

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