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The structure of the mouse ADAT2/ADAT3 complex reveals the molecular basis for mammalian tRNA wobble adenosine-to-inosine deamination.

Ramos-Morales E, Bayam E, Del-Pozo-Rodríguez J, Salinas-Giegé T, Marek M, Tilly P, Wolff P, Troesch E, Ennifar E, Drouard L, Godin JD, Romier C
Nucleic Acids Res 49 6529-6548 (2021)
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Cited: 9 times
EuropePMC logo PMID: 34057470

Abstract

Post-transcriptional modification of tRNA wobble adenosine into inosine is crucial for decoding multiple mRNA codons by a single tRNA. The eukaryotic wobble adenosine-to-inosine modification is catalysed by the ADAT (ADAT2/ADAT3) complex that modifies up to eight tRNAs, requiring a full tRNA for activity. Yet, ADAT catalytic mechanism and its implication in neurodevelopmental disorders remain poorly understood. Here, we have characterized mouse 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 in ADAT2 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.

Articles - 7nz7 mentioned but not cited (2)

  1. The structure of the mouse ADAT2/ADAT3 complex reveals the molecular basis for mammalian tRNA wobble adenosine-to-inosine deamination. Ramos-Morales E, Bayam E, Del-Pozo-Rodríguez J, Salinas-Giegé T, Marek M, Tilly P, Wolff P, Troesch E, Ennifar E, Drouard L, Godin JD, Romier C. Nucleic Acids Res 49 6529-6548 (2021)
  2. Structural basis for sequence-independent substrate selection by eukaryotic wobble base tRNA deaminase ADAT2/3. Dolce LG, Zimmer AA, Tengo L, Weis F, Rubio MAT, Alfonzo JD, Kowalinski E. Nat Commun 13 6737 (2022)


Reviews citing this publication (3)

  1. The life and times of a tRNA. Phizicky EM, Hopper AK. RNA 29 898-957 (2023)
  2. The occurrence, characteristics, and adaptation of A-to-I RNA editing in bacteria: A review. Liao W, Nie W, Ahmad I, Chen G, Zhu B. Front Microbiol 14 1143929 (2023)
  3. Engineered deaminases as a key component of DNA and RNA editing tools. Budzko L, Hoffa-Sobiech K, Jackowiak P, Figlerowicz M. Mol Ther Nucleic Acids 34 102062 (2023)

Articles citing this publication (4)

  1. The thiolation of uridine 34 in tRNA, which controls protein translation, depends on a [4Fe-4S] cluster in the archaeum Methanococcus maripaludis. Bimai O, Legrand P, Ravanat JL, Touati N, Zhou J, He N, Lénon M, Barras F, Fontecave M, Golinelli-Pimpaneau B. Sci Rep 13 5351 (2023)
  2. ADATscan - A flexible tool for scanning exomes for wobble inosine-dependent codons reveals a neurological bias for genes enriched in such codons in humans and mice. Longan ER, Ramos J, Fu D. MicroPubl Biol 2023 (2023)
  3. Amphioxus adenosine-to-inosine tRNA-editing enzyme that can perform C-to-U and A-to-I deamination of DNA. Gao Z, Jiang W, Zhang Y, Zhang L, Yi M, Wang H, Ma Z, Qu B, Ji X, Long H, Zhang S. Commun Biol 6 744 (2023)
  4. Codon usage pattern of the ancestor of green plants revealed through Rhodophyta. Yao H, Li T, Ma Z, Wang X, Xu L, Zhang Y, Cai Y, Tang Z. BMC Genomics 24 538 (2023)


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