DEVELOPMENT TO INFECTIVITY IN TRYPANOSOMA CRUZI INDUCED BY AN RNA-BINDING PROTEIN THROUGH TRANSLATIONAL REPRESSION

MARÍA ALBERTINA ROMANIUK; ALEJANDRO CASSOLA; ALBERTO C. FRASCH

Ciudad de Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS - LIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN BIOQUÍMICA Y BIOLOGÍA MOLECULAR (SAIB); 2017

Gene expression regulation is crucial for cell survival and differentiation.Trypanosomes, protozoan parasites of medical importance,rely mainly on posttranscriptional mechanisms to differentiate andreplicate in insect vectors and vertebrate hosts. RNA binding proteins(RBPs), which associate to the 3?-UTR of mature mRNAs, arethought to orchestrate master developmental programs for theseprocesses to happen. Yet, the molecular mechanisms by whichdifferentiation occurs remain largely unexplored for these humanpathogens. Here, we show that a small increase in the levels ofthe RBP TcUBP1 can recapitulate parasite differentiation in Trypanosomacruzi, the parasite responsible for Chagas disease in theAmericas. Ectopic inducible expression of TcUBP1 in non-infectiousstages (epimastigotes) promoted the differentiation into infectivemetacyclic trypomastigotes. This transformation included repositioningof the kinetoplast, the expression of a virulence factor suchas trans-sialidase and growth arrest, without affecting cell viability.Moreover, TcUBP1-derived metacyclic trypomastigotes proved to beinfective in cell culture. Using a 3? UTR tethering approach we wereable to show that ectopic expression of TcUBP1 promotes translationalrepression, which was confirmed by a global reduction intranslation rates. Furthermore, expression of mutated and truncated forms of TcUBP1 revealed the importance of low complexity (LC)regions for the induced development to infectivity. Collectively, ourresults show that an RBP has a central role in the differentiation ofT. cruzi epimastigotes to infective metacyclic trypomastigotes, offeringinsights of a translational repression mechanism involving LCsequences.