Abstract
Human peroxiredoxin 5 (PRDX5) gene, encodes a member of the peroxiredoxin family of antioxidant enzymes, which reduces hydrogen peroxide and alkyl hydroperoxides. Apart from its antioxidant function, PRDX5 is also predicted to have a role in the regulation of gene transcription. The predicted PRDX5 protein has a strong mitochondrial localization signal how the protein goes to the nucleus and acts as transcription factor is not known. The PRDX5 mRNA has two in‐frame AUG codons, translation from the first ‘AUG’ results in the full length protein (~24 kDa) and translation from second ‘AUG’ results in a shorter protein (~18 kDa). We found that the shorter form of PRDX5 which lacks the N‐terminal mitochondrial import signal is located in the nucleus and regulates BRCA2 gene expression in human breast cancer cells in a redox dependent manner. Here we report a miRNA mediated mechanism for the regulation of alternative translation initiation of PRDX5 mRNA. The microRNA hsa‐miR 3185 has a strong binding site within the two in‐frame AUG codon of the PRDX5 ORF. Increase in the oxidation state leads to an increased expression of hsa‐miR‐3185. Increase amount of miR‐3185 leads to an increase in short form of PRDX5 translation from the second AUG perhaps by blocking the translation initiation from the first AUG codon. To our knowledge this is the first report of regulation of alternative translation initiation of a human gene by a microRNA.Grant Funding Source: Supported by the DOD‐CDMRP BCRP Grants W81XWH‐06‐1‐0466, W81XWH‐08‐1‐0446, BC086542, and the Susan G
Published Version
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