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.
Highlights
The genetic code is degenerate, as the number of amino acids coded is smaller than the number of possible codons, and multiple codons can code for the same amino acid
We have recently shown that codon bias and transfer RNAs (tRNA) gene copy number in eukaryotes were influenced by the emergence of heterodimeric adenosine deaminases acting on tRNAs (ADAT), which deaminate
ADAT-aa are defined as those amino acids that are charged to tRNAs that can be modified by ADAT
Summary
The genetic code is degenerate, as the number of amino acids coded is smaller than the number of possible codons, and multiple codons can code for the same amino acid. We have used two different methods to determine the distribution of TAPS-, and LIVR-coding triplets in the human genome: a half-gene analysis, and a running-window approach Those transcripts with a significantly increased proportion of these triplets have been analyzed for their composition in ADAT-preferred codons, to test if these are enriched with respect to G-ended codons in these proteins. We included both TAPS and LIVR in the search for proteins highly enriched in ADAT-related codons, we find that the most biased human protein sequences in this regard are only enriched in TAPS In these sequences only the triplets for TAPS are enriched for ADAT-dependent codons, indicating that the activity of ADAT may be important for the translation of gene regions coding for long stretches of ADAT-aa. Our results hint at the possibility that the emergence of ADAT allowed eukaryotic cells to produce highly repetitive protein sequences that bacterial or archaeal ribosomes may be unable to translate due to the absence of I34-containing tRNAs in these organisms
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
