Gleason, A.C.; Ghadge, G.; Sonobe, Y.; Roos, R.P. Kozak Similarity Score Algorithm Identifies Alternative Translation Initiation Codons Implicated in Cancers. Int. J. Mol. Sci.2022, 23, 10564.
Gleason, A.C.; Ghadge, G.; Sonobe, Y.; Roos, R.P. Kozak Similarity Score Algorithm Identifies Alternative Translation Initiation Codons Implicated in Cancers. Int. J. Mol. Sci. 2022, 23, 10564.
Gleason, A.C.; Ghadge, G.; Sonobe, Y.; Roos, R.P. Kozak Similarity Score Algorithm Identifies Alternative Translation Initiation Codons Implicated in Cancers. Int. J. Mol. Sci.2022, 23, 10564.
Gleason, A.C.; Ghadge, G.; Sonobe, Y.; Roos, R.P. Kozak Similarity Score Algorithm Identifies Alternative Translation Initiation Codons Implicated in Cancers. Int. J. Mol. Sci. 2022, 23, 10564.
Abstract
Ribosome profiling and mass spectroscopy have identified canonical and noncanonical translation initiation codons (TICs) that are upstream of the main translation initiation site and used to translate oncogenic proteins. Here, we use a Kozak Similarity Score algorithm to find that nearly all of these TICs have flanking nucleotides closely matching the Kozak sequence. Remarkably, the nucleotides flanking alternative noncanonical TICs are frequently closer to the Kozak sequence than the nucleotides flanking TICs used to translate the gene’s main protein. Of note, the 5’ untranslated region (5‘UTR) of cancer-associated genes with an upstream TIC tend to be significantly longer than the same region in genes not associated with cancer. The presence of a longer than typical 5’UTR increases the likelihood of ribosome binding to upstream noncanonical TICs, and may be a distinguishing feature of a number of genes overexpressed in cancer. Noncanonical TICs that are located in the 5’UTR, although thought disadvantageous and suppressed by evolution, may translate oncogenic proteins because of their flanking nucleotides
Keywords
translation initiation; canonical and noncanonical translation initiation codons; protein translation; oncogene; oncogenesis; tumorigenesis; cancer
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
