Distal nucleotides affect the rate of stop codon read-through

LUCIANA I. ESCOBAR; ANDRÉS M. ALONSO; JORGE R. RONDEROS; LUIS DIAMBRA

Quantitative Biology

Higher Education Press

Año: 2022

A key step in gene expression is the recognition of the stop codon to terminate translation at the correctposition. However, it has been observed that ribosomes can misinterpret the stop codon and continue the translationin the 3′UTR region. This phenomenon is called stop codon read-through (SCR). It has been suggested that theseevents would occur on a programmed basis, but the underlying mechanisms are still not well understood.Methods: Here, we present a strategy for the comprehensive identification of SCR events in the Drosophilamelanogaster transcriptome by evaluating the ribosomal density profiles. The associated ribosomal leak rate wasestimated for every event identified. A statistical characterization of the frequency of nucleotide use in the proximalregion to the stop codon in the sequences associated to SCR events was performed.Results: The results show that the nucleotide usage pattern in transcripts with the UGA codon is different from thepattern for those transcripts ending in the UAA codon, suggesting the existence of at least two mechanisms that couldalter the translational termination process. Furthermore, a linear regression models for each of the three stop codonswas developed, and we show that the models using the nucleotides at informative positions outperforms those modelsthat consider the entire sequence context to the stop codon