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Invasion and Replication Strategies of Pathogenes
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SP B10

Cis and trans mRNA Splicing in Trypanosomes:
Functional Analysis of Interactions
between RNA and Protein Components


Prof. Dr. Albrecht Bindereif
Institut für Biochemie (FB 08), Justus-Liebig-Universität, Gießen



Summary

Trans mRNA splicing is an essential step in the expression of all protein-coding genes in trypanosomes. As a result, all mRNAs carry a short, non-coding Spliced Leader (SL) sequence at their 5’ end, which is derived from the SL RNA. At least in the case of the poly(A) polymerase gene there is also an internal intron, which is removed by cis splicing. This makes the parallel processing of the polycistronic primary transcript by both cis and trans splicing necessary. The U1 small nuclear RNP (snRNP) was recently discovered and characterized as a cis-splicing specific component. Based on our previous work on the function and biochemical organization of trans-splicing factors we will focus in the next grant period (2006-08) on the following topics:
  • The trans-spliceosomal SL RNP from T.brucei: identification of SL RNP-specific proteins and their functional analysis
  • Characterization of other, trypanosome-specific components of the splicing machinery, in particular of the unusual U2 snRNP; relevance for recognition of the splice sites
  • Genome-wide identification of novel genes with internal introns, using an experimental SELEX approach
As an experimental system we use primarily Trypanosoma brucei, where the relevant molecular-genetic approaches and the genome project are most advanced.
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