Characterization of ADAT2/3 molecules in Trypanosoma cruzi and regulation of mucin gene expression by tRNA editing. Issue 4 (25th February 2022)

• Record Type: Journal Article
• Authors: Bertotti, Santiago; Fleming, Ian; Cámara, María de los Milagros; Centeno Cameán, Camila; Carmona, Santiago J.; Agüero, Fernán; Balouz, Virginia; Zahn, Astrid; Di Noia, Javier M.; Alfonzo, Juan D.; Buscaglia, Carlos A.
• Is Part Of: Biochemical journal. Volume 479:Issue 4(2022)
• Page Start: 561
• Page End: 580
• Publication Date: 2022-02-25
• Subjects: adenosine deaminases -- mucins -- RNA editing -- trypanosomes; Biochemistry -- Periodicals; 572
• DOI: 10.1042/BCJ20210850
• Languages: English
• ISSNs: 0264-6021

Abstract

Abstract : Adenosine-to-inosine conversion at position 34 (A34 -to-I) of certain tRNAs is essential for expanding their decoding capacity. This reaction is catalyzed by the adenosine deaminase acting on tRNA (ADAT) complex, which in Eukarya is formed by two subunits: ADAT2 and ADAT3. We herein identified and thoroughly characterized the ADAT molecules from the protozoan pathogen Trypanosoma cruzi, the causative agent of Chagas Disease. Tc ADAT2 and Tc ADAT3 spontaneously form a catalytically active complex, as shown by expression in engineered bacteria and/or by the increased ex vivo tRNA A-to-I deamination activity of T. cruzi epimastigotes overexpressing Tc ADAT subunits. Importantly, enhanced Tc ADAT2/3 activity in transgenic parasites caused a shift in their in vivo tRNA Thr AGU signature, which correlated with significant changes in the expression of the Thr-rich Tc SMUG proteins. To our knowledge, this is the first evidence indicating that T. cruzi tRNA editing can be modulated in vivo, in turn post-transcriptionally changing the expression of specific genes. Our findings suggest tRNA editing/availability as a forcible step in controlling gene expression and driving codon adaptation in T. cruzi . Moreover, we unveil certain differences between parasite and mammalian host tRNA editing and processing, such as cytosine-to-uridine conversion at position 32 of tRNA Thr AGU in T. cruzi, that may be exploited for the identification of novel druggable targets of intervention.