Identification of the pre-mRNA splicing protein U2AF35 in the opportunistic fungus Pneumocystis carinii
Abstract number: P735
Thomas C., Sanyal B., Vohra P.
The opportunistic fungus Pneumocystis carinii (PC) is an intractable organism responsible for severe pneumonia in patients with AIDS or other immunosuppressive conditions. PC is phylogenetically similar to the non-pathogenic yeasts S. cerevisiae and S. pombe. The regulation of gene function is a complex process critical to the survival of eukaryotes, and thus presents potential targets for novel therapy. Pre-mRNA processing with removal of intervening sequences (introns) is an important step in gene regulation. The assembly of multiple proteins on small nuclear RNA occurs in the spliceosome. Although many components of this molecular machinery is conserved in eukaryotes, there are many significant differences between S. cerevisiae, S. pombe and mammals. The process of gene regulation in PC is unknown. We have previously reported that PC genes contain multiple small introns, yet lack features found in S. cerevisiae and S. pombe (Infection and Immunity, Nov. 1999, p. 61576160). Here we report the identification and cloning of the PCU2AF35 gene, encoding a critical splicosomal protein required for processing the 3' end of the intron. PCU2AF35 is a 621-bp ORF encoding a predicted 206 amino acid protein. The predicted molecular weight is 24.1 kDa, similar to S. pombe U2AF35. PCU2AF35 contains a conserved RNA recognition motif (RRM) postulated to bind RNA sequences. PCU2AF35 is most homologous to S. pombe U2AF35 (72% identity). We have expressed this gene as a recombinant protein to determine its function in PC intron removal. Our investigations may provide new insights into the pathogenesis of PC and potential new therapeutics for treating PC pneumonia through identification of mechanisms involved in PC life cycle regulation.
Supported by NIH grant 2R01 AI-48409 to CFT.
|Session name:||18th European Congress of Clinical Microbiology and Infectious Diseases|
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