Adat2, part of the adenosine deaminase acting on tRNA (ADAT) complex, is crucial for the adenosine-to-inosine (A-to-I) conversion at position 34 (A34-to-I) of certain tRNAs in eukaryotes. This conversion expands tRNA decoding capacity and is essential for proper translation. The ADAT complex in Eukarya consists of two subunits, Adat2 and Adat3 [1,2,4].

In Trypanosoma cruzi, the TcAdat2 and TcAdat3 form a catalytically active complex. Enhanced TcAdat2/3 activity can modulate tRNA editing in vivo, leading to changes in the expression of Thr-rich TcSMUG proteins, suggesting tRNA editing as a step in controlling gene expression in this pathogen [1].

In yeast, the crystal structure of the ScAdat2/3 heterodimer reveals its molecular assembly and substrate recognition mechanism. ScAdat3 has accessory domains, and its C-terminus blocks tRNA entry into its pseudo-active site [2].

In mammals, mutations in Adat3, a subunit of the Adat2/Adat3 complex, are associated with neurodevelopmental disorders. Maintaining proper Adat2/Adat3 catalytic activity is required for correct radial migration of projection neurons in the developing mouse cortex. Variants in Adat3 can disrupt the activity of the Adat2/Adat3 complex, affecting tRNA editing and abundance [3].

In human studies, pathogenic Adat3 variants can be rescued by overexpressing the Adat2 catalytic subunit, highlighting the importance of the Adat2/Adat3 complex in maintaining proper levels of wobble inosine modification in tRNA [5].

In conclusion, Adat2, as part of the Adat2/Adat3 complex, plays a vital role in tRNA editing, which is essential for translation. Studies using various models, including those related to Trypanosoma cruzi, yeast, mouse, and human cells, have revealed its significance in processes like gene expression control in pathogens and neurodevelopment in mammals. Understanding Adat2 function contributes to insights in areas such as infectious diseases caused by Trypanosoma cruzi and neurodevelopmental disorders in humans.