TRANSLATIONAL CONTROL IN TRYPANOSOMATIDS

MARIA DE LOS MILAGROS CAMARA; SANTIAGO BERTOTTI; SANTIAGO CARMONA; CARLOS BUSCAGLIA

Mar del Plata

Congreso; X Congreso de Protozoologia y Enfermedades Parasitarias; 2014

Sociedad Argentina de Protozologia

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. TcSMUG is a multiple member family of Thr-rich mucins genes, composed of two groups of genes, named L and S, organized in independent tandem arrays and differing in the structure of their genomic loci. One notable feature is that TcSMUGL products in contrast to TcSMUGS show substantial differences in their expression levels among parasites stocks. In order to understand the variability in the expression of TcSMUGL we analyzed the secondary structure of the 3´UTR of TcSMUG L mRNAs for the Adriana and CL Brener strain revealing very minor inter-strain differences; suggesting that the observed expression variations may not respond to post-transcriptional mechanisms. Consequently we calculated TcSMUG L codon bias for both strains obtaining inter-strain distortions in the TcSMUG L usage for four codons: Thr(ACT), Val(GTT), Leu(CTT) and Leu(TTG). No codon significant inter-strain distortions were found for TcSMUG S genes. These results suggest that the variability in expression of TcSMUG L could be due to differences in codon bias. Furthermore 3 out of 4 codons displaying significant inter-strain distortions in our analysis; Thr(ACT), Val(GTT) and Leu(CTT) are affected by anticodon tRNA editing. In vivo editing analysis revealed significant inter-strain differences in the editing profile for the tRNAThrAGU isoacceptor, which decodes the inter-strain biased codon Thr(ACT). Finally overexpression of tRNA editing deaminases lead to an increase in the levels of tRNAThr editing and significant changes in the expression profile of TcSMUG L proteins Together these findings suggest a mechanism of gene expression regulation that relies on the efficient interaction of codons and anticodons.