Author:
Roura Frigolé Helena,Camacho Noelia,Castellví Coma Maria,Fernández-Lozano Carla,García-Lema Jorge,Rafels-Ybern Àlbert,Canals Albert,Coll Miquel,Ribas de Pouplana Lluís
Abstract
Adenosine deaminase acting on transfer RNA (ADAT) is an essential eukaryotic enzyme that catalyzes the deamination of adenosine to inosine at the first position of tRNA anticodons. Mammalian ADATs modify eight different tRNAs, having increased their substrate range from a bacterial ancestor that likely deaminated exclusively tRNAArg. Here we investigate the recognition mechanisms of tRNAArg and tRNAAla by human ADAT to shed light on the process of substrate expansion that took place during the evolution of the enzyme. We show that tRNA recognition by human ADAT does not depend on conserved identity elements, but on the overall structural features of tRNA. We find that ancestral-like interactions are conserved for tRNAArg, while eukaryote-specific substrates use alternative mechanisms. These recognition studies show that human ADAT can be inhibited by tRNA fragments in vitro, including naturally occurring fragments involved in important regulatory pathways.
Funder
PRB3
Spanish Ministry of Economy and Competitiveness
Publisher
Cold Spring Harbor Laboratory
Cited by
12 articles.
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