Faculty of Medicine of Strasbourg, France “ The structure of the mouse ADAT2/ADAT3 complex reveals the molecular basis for mammalian tRNA wobble adenosine-to-inosine deamination”
Nucleic acids research, 49(11), 6529–6548. https://doi.org/10.1093/nar/gkab436
Ramos-Morales, E., Bayam, E., Del-Pozo-Rodríguez, J., Salinas-Giegé, T., Marek, M., T illy, P., Wolff, P., Troesch, E., Ennifar, E., Drouard, L., Godin, J. D., & Romier, C.
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Elizabeth Ramos Morales, 33 years old, obtained the Bachelor’s degree in Molecular and Cellular Biology and the Master’s degree in IntegratedMolecular and Cellular Biology at Strasbourg University. She got her PhD degree in 2021 in Molecular and Cellular Aspects of Biology, which wasperformed in the laboratory of Dr. Romier («Molecular basis of chromatin and Transcription regulation» in the department of Integrated Structural Biologyat the IGBMC). Being interested in both fundamental and applied research to understand the molecular mechanisms that lead to the development ofdiseases, she decided to join the Faculty of Medicine to continue her studies. Her goal is to acquire complementary expertise so that to be able to offer, through her researches, better and more adequate treatments to patients.
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Résumé de l'article
Post-transcriptional modification of tRNA wobble adenosine into inosine is crucial for decoding multiple mRNA codons by a single tRNA. The eukaryoticwobble adenosine-to-inosine modification is catalyzed by the ADAT (ADAT2/ADAT3) complex that modifies up to eight tRNAs, requiring a full tRNA foractivity. Yet, ADAT catalytic mechanism and its implication in neurodevelopmental disorders remain poorly understood. Here, we have characterizedmouse ADAT and provide the molecular basis for tRNAs deamination by ADAT2 as well as ADAT3 inactivation by loss of catalytic and tRNA-binding determinants. We show that tRNA binding and deamination can vary depending on the cognate tRNA but absolutely rely on the eukaryote-specific ADAT3 N-terminal domain. This domain can rotate with respect to the ADAT catalytic domain to present and position the tRNA anticodon-stem-loop correctly inADAT2 active site. A founder mutation in the ADAT3 N-terminal domain, which causes intellectual disability, does not affect tRNA binding despite the structural changes it induces but most likely hinders optimal presentation of the tRNA anticodon-stem-loop to ADAT2.
