PROTEIN SYNTHESIS IN LEISHMANIA

点击翻译按钮获取中文摘要

DESCRIPTION (provided by the applicant): Human leishmaniasis is caused by the Leishmania spp. In this protozoan parasite, initiation of transcription is not a major mode of gene regulation. Consequently, post-transcriptional pathways for controlling protein expression, which is critical for virulence, are of utmost importance. Untranslated regions of mature mRNAs can have major effects on several aspects of mRNA metabolism in other organisms. Our long-term goals are to determine general principles by which initiation-codon proximal sequences influence translation and/or mRNA stability in Leishmania. We performed bioinformatic analysis of two hundred Leishmania genes, and discovered hexamer nucleotides that were popular in regions close to translation initiation codons. Further analysis revealed that the hexamers were components of five extended sequence motifs that might be Leishmania equivalents of "post-transcriptional operons" recently describe, vertebrates. We hypothesize that the Leishmania sequence motifs coordinate expression of genes af, naturation of pre-mRNAs. To test the theories (above) representative sequence motifs will be cloned upstream of reporter genes, electroporated into Leishmania, and stable cell lines of parasites selected. The influence of the motifs on mRNA stability and/or translation will be determined in promastigote, metacyclic, and amastigote developmental stages. These studies are likely to lead to discovery of novel regulators of mRNA metabolism, thereby furthering our understanding of post-transcriptional gene regulation in Leishmania.