Kozak Similarity Score Algorithm Identifies Alternative Translation Initiation Codons Implicated in Cancers
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. There have previously been conflicting reports about the patterns of nucleotide...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/18/10564 |
| _version_ | 1797487237986779136 |
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| author | Alec C. Gleason Ghanashyam Ghadge Yoshifumi Sonobe Raymond P. Roos |
| author_facet | Alec C. Gleason Ghanashyam Ghadge Yoshifumi Sonobe Raymond P. Roos |
| author_sort | Alec C. Gleason |
| collection | DOAJ |
| description | 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. There have previously been conflicting reports about the patterns of nucleotides that surround noncanonical TICs. 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 by some to be disadvantageous and suppressed by evolution, may translate oncogenic proteins because of their flanking nucleotides. |
| first_indexed | 2024-03-09T23:45:49Z |
| format | Article |
| id | doaj.art-719497a4ae66427c8e158a73734b3631 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:45:49Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-719497a4ae66427c8e158a73734b36312023-11-23T16:43:55ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181056410.3390/ijms231810564Kozak Similarity Score Algorithm Identifies Alternative Translation Initiation Codons Implicated in CancersAlec C. Gleason0Ghanashyam Ghadge1Yoshifumi Sonobe2Raymond P. Roos3Department of Neurology, University of Chicago Medical Center, Chicago, IL 60637, USADepartment of Neurology, University of Chicago Medical Center, Chicago, IL 60637, USADepartment of Neurology, University of Chicago Medical Center, Chicago, IL 60637, USADepartment of Neurology, University of Chicago Medical Center, Chicago, IL 60637, USARibosome 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. There have previously been conflicting reports about the patterns of nucleotides that surround noncanonical TICs. 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 by some to be disadvantageous and suppressed by evolution, may translate oncogenic proteins because of their flanking nucleotides.https://www.mdpi.com/1422-0067/23/18/10564translation initiationcanonical and noncanonical translation initiation codonsprotein translationoncogeneoncogenesistumorigenesis |
| spellingShingle | Alec C. Gleason Ghanashyam Ghadge Yoshifumi Sonobe Raymond P. Roos Kozak Similarity Score Algorithm Identifies Alternative Translation Initiation Codons Implicated in Cancers International Journal of Molecular Sciences translation initiation canonical and noncanonical translation initiation codons protein translation oncogene oncogenesis tumorigenesis |
| title | Kozak Similarity Score Algorithm Identifies Alternative Translation Initiation Codons Implicated in Cancers |
| title_full | Kozak Similarity Score Algorithm Identifies Alternative Translation Initiation Codons Implicated in Cancers |
| title_fullStr | Kozak Similarity Score Algorithm Identifies Alternative Translation Initiation Codons Implicated in Cancers |
| title_full_unstemmed | Kozak Similarity Score Algorithm Identifies Alternative Translation Initiation Codons Implicated in Cancers |
| title_short | Kozak Similarity Score Algorithm Identifies Alternative Translation Initiation Codons Implicated in Cancers |
| title_sort | kozak similarity score algorithm identifies alternative translation initiation codons implicated in cancers |
| topic | translation initiation canonical and noncanonical translation initiation codons protein translation oncogene oncogenesis tumorigenesis |
| url | https://www.mdpi.com/1422-0067/23/18/10564 |
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