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Yousuf A. Khan edited this page Jan 12, 2020 · 18 revisions

Evidence for a novel overlapping coding sequence in POLG initiated at a CUG start codon

Introduction

The code presented here was used to discover and characterize a novel overlapping ORF in the mRNA of POLG (ORF-Y) and a second, further upstream ORF (ORF-Z) that is likely regulatory in modulating translation between ORF-Y and the main ORF. The work is of interest for two main reasons

  1. Overlapping ORFs in the human genome of such length are extremely rare. ORF-Y in POLG may represent the longest bonafide overlapping ORF in the human genome.

  2. POLG is of significant clinical relevance. Many mutations have been mapped across its mRNA that link to mitochondrial disease. Given the extent of overlap with ORF-Y, it is possible that the mechanism of action of some of these mutations is a combined effect exerted on both the protein products of main ORF and ORF-Y.

Breakdown of Figures

The following will cogently run the readers through how the analysis of each of the figures was conducted with the accompanying code.

Figure 1

Panel a - Schematic of POLG mRNA: Generated in Powerpoint/Adobe Illustrator using https://uswest.ensembl.org/Homo_sapiens/Transcript/Summary?g=ENSG00000140521;r=15:89316305-89334795;t=ENST00000268124 as a guide

Panel b - PhyloCSF analysis of POLG: PhyloCSF is well documented and more information can be found at https://github.com/mlin/PhyloCSF/wiki

Figure 2

The accompanying code is available

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