title: Distribution of ADAT-Dependent Codons in the Human Transcriptome.
abstract: Nucleotide modifications in the anticodons of transfer RNAs (tRNA) play a central role in translation efficiency, fidelity, and regulation of translation, but, for most of these modifications, the details of their function remain unknown. The heterodimeric adenosine deaminases acting on tRNAs (ADAT2-ADAT3, or ADAT) are enzymes present in eukaryotes that convert adenine (A) to inosine (I) in the first anticodon base (position 34) by hydrolytic deamination. To explore the influence of ADAT activity on mammalian translation, we have characterized the human transcriptome and proteome in terms of frequency and distribution of ADAT-related codons. Eight different tRNAs can be modified by ADAT and, once modified, these tRNAs will recognize NNC, NNU and NNA codons, but not NNG codons. We find that transcripts coding for proteins highly enriched in these eight amino acids (ADAT-aa) are specifically enriched in NNC, NNU and NNA codons. We also show that the proteins most enriched in ADAT-aa are composed preferentially of threonine, alanine, proline, and serine (TAPS). We propose that the enrichment in ADAT-codons in these proteins is due to the similarities in the codons that correspond to TAPS.
authors.affiliation: Institute for Research in Biomedicine (IRB), Parc Cientific de Barcelona, C/Baldiri Reixac 10, 08028 Bacelona, Spain. albert.rafels@irbbarcelona.org.
authors.forename: Àlbert
authors.initials: À
authors.lastname: Rafels-Ybern
authors.affiliation: Institute for Research in Biomedicine (IRB), Parc Cientific de Barcelona, C/Baldiri Reixac 10, 08028 Bacelona, Spain. camille.stephan@irbbarcelona.org.
authors.forename: Camille Stephan-Otto
authors.initials: CS
authors.lastname: Attolini
authors.affiliation: Institute for Research in Biomedicine (IRB), Parc Cientific de Barcelona, C/Baldiri Reixac 10, 08028 Bacelona, Spain. lluis.ribas@irbbarcelona.org.|Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluís Companys 23, 08010 Barcelona, Spain. lluis.ribas@irbbarcelona.org.
authors.forename: Lluís
authors.initials: L
authors.lastname: Ribas de Pouplana
mesh_terms: D000659:AMP Deaminase / Q000378:metabolism*; D003062:Codon / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015894:Genome, Human; D006801:Humans; D020543:Proteome / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012343:RNA, Transfer / Q000378:metabolism; D059467:Transcriptome
chemical_list: D003062:Codon; D020543:Proteome; D012343:RNA, Transfer; D000659:AMP Deaminase
keywords: ADAT2-ADAT3; codon degeneracy; tRNA gene copy number; tRNA modification enzymes