Adat2, part of the adenosine deaminase acting on tRNA (ADAT) family, is a key catalytic subunit. It forms a heterodimer with Adat3, and this complex catalyzes the adenosine - to - inosine (A - to - I) editing in the anticodons of tRNAs. This modification is crucial for wobble base - pairing during translation, expanding tRNA decoding capacity and thus playing an essential role in protein biosynthesis [1,2,3,4,5,6,7,8,9].

In Trypanosoma cruzi, enhanced TcAdat2/3 activity led to a shift in the in vivo tRNAThrAGU signature and changes in the expression of Thr - rich TcSMUG proteins, suggesting tRNA editing/availability as a step in controlling gene expression [2]. In mouse models, maintaining proper Adat2/3 catalytic activity is required for correct radial migration of projection neurons in the developing cortex. Mutations in Adat3, the non - catalytic subunit, disrupt the activity of the Adat2/Adat3 complex, impair neuronal migration, and are associated with severe neurodevelopmental disorders [3]. In humans, mutations in Adat3, such as the V144M mutation, affect Adat2/3 complex activity, reducing wobble inosine in certain tRNAs and causing autosomal recessive intellectual disability [7]. Also, novel Adat3 variants that impair adenosine deaminase activity due to altered interaction with Adat2 can be rescued by overexpressing the Adat2 catalytic subunit [8].

In conclusion, Adat2, as part of the Adat2/3 complex, is essential for tRNA A - to - I editing, which impacts translation and protein biosynthesis. Model - based research, especially in mouse models and human cell lines, has revealed its crucial role in neurodevelopment, with implications for understanding and potentially treating neurodevelopmental disorders such as intellectual disability [2,3,7,8].