Translational control of mucin expression in T. cruzi

MARIA DE LOS MILAGROS CAMARA; SANTIAGO BERTOTTI; VIRGINIA BALOUZ; CARLOS BUSCAGLIA

Trieste

Simposio; ICGEB 2nd Post-EURASNET Symposium ?RNA Alternative Splicing?; 2013

ICEGB TRIESTE

The protozoan T. cruzi is the etiological agent of Chagas disease, a major public health issue in Latin America. Due to its predominant clonal proliferation, this species is composed by multiple ?discrete typing units? displaying considerable genetic diversity. Comparative analysis led to the identification of quantitative/qualitative differences on the expression of multiple molecules including well-established virulence factors such as trans-sialidases and mucins. It has been explored that control of gene expression in T. cruzi is essentially concerted by post-transcriptional mechanisms which would be reinforced by epigenetic factors and/or translational control. TcSMUG is an homogeneous multiple member family of Thr-rich mucins genes. Along their transit to the parasite surface, the hydroxyl groups of some of the Thr residues are further elaborated with short O-linked oligosaccharide chains that are thought to confer protective, adhesive and functional properties to the mature TcSMUG products. TcSMUG is composed of two groups of genes, named L and S, organized in independent tandem arrays and differing in the structure of their genomic loci. Both groups are co-expressed in the epimastigotes stage, and share structural homologies, but present different functions and post-transcriptional modifications. One notable feature is that TcSMUGL products in contrast to TcSMUGS show substantial differences in their expression levels among parasites stocks. In the present work we explore the molecular basis which controls TcSMUG L inter-stock differential expression variability which would be relying in a translational mechanism operating on TcSMUGL mRNAs which would depend on stock specific codon usage and differences in the overall ?tRNA signature? (tRNAs gene transcription, tRNA maduration and tRNA editing)