TcUBP1 RNA-binding protein induces up regulation of a surface glycoprotein RNA regulon and promotes infectivity of the human parasite Trypanosoma cruzi?

SABALETTE KB; CASSOLA A; DE GAUDENZI JG; ROMANIUK A; FRASCH AC; NOÉ G; CAMPO VA

Congreso; LIV Reunión SAIB 2018; 2018

In the absence of transcription initiation regulation, organized subsets of Trypanosoma cruzi RNAs must be post-transcriptionally co-regulated in response to extracellular signals. Hence regulons, functionally linked mRNAs modulated by trans-acting factors, regain importance. The RNA-binding protein TcUBP1 binds a large variety of transcripts including trans-sialidase/trans-sialidaselike (TcS) superfamily, a polymorphic group of surface glycoproteins preferentially expressed in the infective forms of the parasite. In vitro RNA-binding assays showed that a 50-nt cis-element highly conserved in the 3?UTR of most TcS family members mediates the interaction with TcUBP1. When steady-state levels of these mRNAs were analyzed by qPCR in replicative non-infective parasites ectopically expressing TcUBP1-GFP, an average of 12-fold increase was observed in comparison to non-induced and GFP induced controls. Moreover, FISH assays revealed that RNA localization of TcS family transcripts change after induction of TcUBP1-GFP to a perinuclear localization, suggesting a subcellular distribution appropriate for RNA translation. Experiments are underway to quantitatively measure these transcript levels in polysomal fractions of both induced and non-induced samples. Finally, cell derived trypomastigotes obtained from epimastigotes expressing TcUBP1-GFP showed a 2-fold increased infectivity comparing to the non-induced controls. Altogether, our results point to a coordinately up-regulation effect of TcS proteins as a response to induction of TcUBP1, thus reflecting a switch towards trypomastigote-form mRNA expression patterns.