Distal nucleotides affect the rate of stop codon read-through

Abstract

Background: A key step in gene expression is the recognition of the stop codon to terminate translation at the correct position. However, it has been observed that ribosomes can misinterpret the stop codon and continue the translation in the 3 ′UTR region. This phenomenon is called stop codon read-through (SCR). It has been suggested that these events 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 Drosophila melanogaster transcriptome by evaluating the ribosomal density profiles. The associated ribosomal leak rate was estimated for every event identified. A statistical characterization of the frequency of nucleotide use in the proximal region 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 the pattern for those transcripts ending in the UAA codon, suggesting the existence of at least two mechanisms that could alter the translational termination process. Furthermore, a linear regression models for each of the three stop codons was developed, and we show that the models using the nucleotides at informative positions outperforms those models that consider the entire sequence context to the stop codon. Conclusions: We report that distal nucleotides can affect the SCR rate in a stop-codon dependent manner.