Trans mRNA splicing in trypanosomes
|Trypanosomes are parasitic protozoa, including species that cause
tropical diseases. In trypanosomes all protein-coding mRNAs are
generated through trans splicing, whereby each protein-coding exon is
joined with a noncoding spliced leader (SL) miniexon. Our interests in
this area focus on the regulation and the mechanism of trans splicing,
and a general goal is to define the differences between the trans
splicing and the conventional cis splicing mechanisms (for example, see
Palfi et al., 2000; Wang et al., 2006). A detailed
understanding should open up new avenues in the fight against
trypanosome-caused diseases, such as the African sleeping sickness or
the Chagas disease. Currently we are adapting genomewide approaches
mentioned above (RNA-Seq; iCLIP) to the trypanosome system. A specific
focus is the detailed study of the role of the trypanosome SMN protein
in the biogenesis of small nuclear ribonucleoproteins, a factor that
when misregulated in the human system results in Spinal Muscular Atrophy
(SMA) disease. The trypanosome system provides here a simple model
system for a disease-relevant splicing factor (Palfi et al., 2009; Jaé et al., 2011).
- Jaé N, Preußer C, Krüger T, Tkacz ID, Engstler M, Michaeli S, Bindereif A. 2011. snRNA-specific role of SMN in trypanosome snRNP biogenesis in vivo.
RNA Biol 8: 90-100.
- Palfi Z, Lücke S, Lahm HW, Lane WS, Kruft V, Bragado-Nilsson E, Séraphin B, Bindereif A. 2000. The spliceosomal snRNP core complex of Trypanosoma brucei: Cloning and functional analysis reveals seven Sm protein constituents.
Proc Natl Acad Sci USA 97: 8967-8972.
- Palfi Z, Jaé N, Preußer C, Kaminska KH, Bujnicki JM, Lee JH, Günzl A, Kambach C, Urlaub H, Bindereif A. 2009. SMN-assisted assembly of snRNP-specific Sm cores in trypanosomes.
Genes Dev 23: 1650-1664.
- Wang P, Palfi Z, Preußer C, Lücke S, Lane WS, Kambach C, Bindereif A. 2006. Sm core variation in spliceosomal small ribonucleoproteins from Trypanosoma brucei.
EMBO J 25: 4513-4523.