Complete motif analysis of sequence requirements for translation initiation at non-AUG start codons
| Autor: | William L Noderer, Alexander J Diaz de Arce, Clifford L. Wang |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
viruses Codon Initiator Genomics Computational biology Biology environment and public health 03 medical and health sciences Mice Eukaryotic translation Start codon Genetics Protein biosynthesis Animals Humans RNA Messenger Nucleotide Motifs Codon Peptide Chain Initiation Translational Base Sequence RNA food and beverages Hep G2 Cells HCT116 Cells Disease etiology Highly sensitive 030104 developmental biology HEK293 Cells Protein Biosynthesis NIH 3T3 Cells Motif (music) K562 Cells Synthetic Biology and Bioengineering HeLa Cells |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 |
| Popis: | The initiation of mRNA translation from start codons other than AUG was previously believed to be rare and of relatively low impact. More recently, evidence has suggested that as much as half of all translation initiation utilizes non-AUG start codons, codons that deviate from AUG by a single base. Furthermore, non-AUG start codons have been shown to be involved in regulation of expression and disease etiology. Yet the ability to gauge expression based on the sequence of a translation initiation site (start codon and its flanking bases) has been limited. Here we have performed a comprehensive analysis of translation initiation sites that utilize non-AUG start codons. By combining genetic-reporter, cell-sorting, and high-throughput sequencing technologies, we have analyzed the expression associated with all possible variants of the -4 to +4 positions of non-AUG translation initiation site motifs. This complete motif analysis revealed that 1) with the right sequence context, certain non-AUG start codons can generate expression comparable to that of AUG start codons, 2) sequence context affects each non-AUG start codon differently, and 3) initiation at non-AUG start codons is highly sensitive to changes in the flanking sequences. Complete motif analysis has the potential to be a key tool for experimental and diagnostic genomics. |
| Databáze: | OpenAIRE |
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