The Expansion of Inosine at the Wobble Position of tRNAs, and Its Role in the Evolution of Proteomes

Rafels-Ybern, Àlbert; Torres, Adrián Gabriel; Camacho, Noelia; Herencia-Ropero, Andrea; Frigolé, Helena Roura; Wulff, Thomas F.; Raboteg, Marina; Bordons, Albert; Grau‐Bové, Xavier; Ruiz‐Trillo, Iñaki; Pouplana, Lluı́s Ribas de

doi:10.1093/molbev/msy245

Cited by 41 publications

(41 citation statements)

References 54 publications

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“…For the same reason, the I modification can be detected in standard RNA-seq experiments based on increased proportion of A-to-G mismatches at known sites of modification when aligned to the reference genome [24], even if a specific sequencing protocol based on selective reaction of inosine to a chemical pre-treatment has been developed to increase detection efficacy [25,68]. In tRNAs, I occurs at position 34 ( Figure 4) in 8 out of 16 eukaryotic tRNAs with ANN anticodon (namely, the AGC, ACG, AAT, AAG, AGG, AGA, AGT, and AAC anticodons) where it is introduced by the ADAT2-ADAT3 heterodimer [65,69,70]. I34 also occurs in bacteria in tRNA Arginine (ACG anticodon) and tRNA Leucine (AAG anticodon), where it is introduced by the tRNA adenosine deaminase A (TadA) homodimer, while it is not present in archaea [70].…”

Section: Adenosine-derived Modificationsmentioning

confidence: 99%

“…In tRNAs, I occurs at position 34 ( Figure 4) in 8 out of 16 eukaryotic tRNAs with ANN anticodon (namely, the AGC, ACG, AAT, AAG, AGG, AGA, AGT, and AAC anticodons) where it is introduced by the ADAT2-ADAT3 heterodimer [65,69,70]. I34 also occurs in bacteria in tRNA Arginine (ACG anticodon) and tRNA Leucine (AAG anticodon), where it is introduced by the tRNA adenosine deaminase A (TadA) homodimer, while it is not present in archaea [70]. Position 34 is the first base of a tRNA anticodon (spanning positions 34-36 in the tRNA sequence), and it is named the "wobble" position due to involvement in flexible base pairing with the third position of a codon in the "codon-anticodon duplex" [7].…”

Section: Adenosine-derived Modificationsmentioning

confidence: 99%

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A Census and Categorization Method of Epitranscriptomic Marks

Mathlin

Pera

Colombo

2020

IJMS

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In the past few years, thorough investigation of chemical modifications operated in the cells on ribonucleic acid (RNA) molecules is gaining momentum. This new field of research has been dubbed “epitranscriptomics”, in analogy to best-known epigenomics, to stress the potential of ensembles of RNA modifications to constitute a post-transcriptional regulatory layer of gene expression orchestrated by writer, reader, and eraser RNA-binding proteins (RBPs). In fact, epitranscriptomics aims at identifying and characterizing all functionally relevant changes involving both non-substitutional chemical modifications and editing events made to the transcriptome. Indeed, several types of RNA modifications that impact gene expression have been reported so far in different species of cellular RNAs, including ribosomal RNAs, transfer RNAs, small nuclear RNAs, messenger RNAs, and long non-coding RNAs. Supporting functional relevance of this largely unknown regulatory mechanism, several human diseases have been associated directly to RNA modifications or to RBPs that may play as effectors of epitranscriptomic marks. However, an exhaustive epitranscriptome’s characterization, aimed to systematically classify all RNA modifications and clarify rules, actors, and outcomes of this promising regulatory code, is currently not available, mainly hampered by lack of suitable detecting technologies. This is an unfortunate limitation that, thanks to an unprecedented pace of technological advancements especially in the sequencing technology field, is likely to be overcome soon. Here, we review the current knowledge on epitranscriptomic marks and propose a categorization method based on the reference ribonucleotide and its rounds of modifications (“stages”) until reaching the given modified form. We believe that this classification scheme can be useful to coherently organize the expanding number of discovered RNA modifications.

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Section: Adenosine-derived Modificationsmentioning

confidence: 99%

Section: Adenosine-derived Modificationsmentioning

confidence: 99%

A Census and Categorization Method of Epitranscriptomic Marks

Mathlin

Pera

Colombo

2020

IJMS

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“…Deamination of A34 to generate inosine is catalyzed in bacteria by TadA (Fig. ), likely evolved from a cytosine deaminase . tRNA Arg ACG is the canonical target of TadA, which is essential in E. coli and other bacteria that use inosine to decode the arginine GCU/C/A codons .…”

Section: Inosine Modificationmentioning

confidence: 99%

“…A recent tRNAome analysis of A34 distribution suggested that some bacteria could expand their use of inosine‐wobbling tRNAs. Indeed, Oenococcus oeni tRNA Leu AAG was shown to contain I34, presumably generated by TadA . Although essential in E. coli , TadA is not widely distributed .…”

Section: Inosine Modificationmentioning

confidence: 99%

Bacterial wobble modifications of NNA‐decoding tRNAs

Nilsson

Alexander

2019

IUBMB Life

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Nucleotides of transfer RNAs (tRNAs) are highly modified, particularly at the anticodon. Bacterial tRNAs that read A‐ending codons are especially notable. The U34 nucleotide canonically present in these tRNAs is modified by a wide range of complex chemical constituents. An additional two A‐ending codons are not read by U34‐containing tRNAs but are accommodated by either inosine or lysidine at the wobble position (I34 or L34). The structural basis for many N34 modifications in both tRNA aminoacylation and ribosome decoding has been elucidated, and evolutionary conservation of modifying enzymes is also becoming clearer. Here we present a brief review of the structure, function, and conservation of wobble modifications in tRNAs that translate A‐ending codons. © 2019 IUBMB Life, 2019 © 2019 IUBMB Life, 71(8):1158–1166, 2019

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“…Correspondingly, tRNA substrate repertoires in the two kingdoms are different. In eukarya, a few tRNAs (seven or eight) with genomically encoded A34 are deaminated by the ADAT2/3 heterodimer [8][9][10][11], whereas in bacteria, the A-to-I editing by TadA is found mostly in tRNA Arg , although recent studies have shown that other tRNA species could be modified as well [12,13]. How eukaryotic ADAT2/3s modify various tRNAs remains an open question.…”

Section: Introductionmentioning

confidence: 99%

Crystal structure of the yeast heterodimeric ADAT2/3 deaminase

et al. 2020

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Background The adenosine-to-inosine (A-to-I) editing in anticodons of tRNAs is critical for wobble base-pairing during translation. This modification is produced via deamination on A34 and catalyzed by the adenosine deaminase acting on tRNA (ADAT) enzyme. Eukaryotic ADATs are heterodimers composed of the catalytic subunit ADAT2 and the structural subunit ADAT3, but their molecular assemblies and catalytic mechanisms are largely unclear. Results Here, we report a 2.8-Å crystal structure of Saccharomyces cerevisiae ADAT2/3 (ScADAT2/3), revealing its heterodimeric assembly and substrate recognition mechanism. While each subunit clearly contains a domain resembling their prokaryotic homolog TadA, suggesting an evolutionary gene duplication event, they also display accessory domains for additional structural or functional purposes. The N-lobe of ScADAT3 exhibits a positively charged region with a potential role in the recognition and binding of tRNA, supported by our biochemical analysis. Interestingly, ScADAT3 employs its C-terminus to block tRNA’s entry into its pseudo-active site and thus inactivates itself for deamination despite the preservation of a zinc-binding site, a mechanism possibly shared only among yeasts. Conclusions Combining the structural with biochemical, bioinformatic, and in vivo functional studies, we propose a stepwise model for the pathway of deamination by ADAT2/3. Our work provides insight into the molecular mechanism of the A-to-I editing by the eukaryotic ADAT heterodimer, especially the role of ADAT3 in catalysis.

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The Expansion of Inosine at the Wobble Position of tRNAs, and Its Role in the Evolution of Proteomes

Cited by 41 publications

References 54 publications

A Census and Categorization Method of Epitranscriptomic Marks

A Census and Categorization Method of Epitranscriptomic Marks

Bacterial wobble modifications of NNA‐decoding tRNAs

Crystal structure of the yeast heterodimeric ADAT2/3 deaminase

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