PRDX6 is a cytosolic member of the peroxiredoxin family of antioxidant proteins, which protect cells from oxidative damage by reducing cellular peroxides. Knockout studies and transgenic overexpression of Prdx6 in mice have demonstrated an important role for this protein in the defense against oxidative stress. Using Northern blotting with various Prdx6 probes, we have revealed the existence of multiple transcripts with distinct tissue distributions and regulation, including the major 1.4-kb transcript highly expressed in liver and lung, and two additional transcripts expressed primarily in liver. We hypothesized that these additional transcripts correspond either to alternative Prdx6 mRNAs or to highly related genes such as the intronless genes Aop2-rs1 and Aop2-rs2. A combination of Northern blotting, RACE, and EST and genomic sequence analysis has determined that all three liver transcripts are derived from the Prdx6 gene, as they are absent in Prdx6-null mice and differ in their 3′ UTRs, suggesting the utilization of different transcription termination signal sequences which we have identified by sequence analysis. We found the Aop2-rs1 gene to be exclusively expressed in testis as a 1.2-kb transcript and have identified putative regulatory elements in its promoter. In contrast, Aop2-rs2 appears not to be expressed in any tissues, although we have evidence for the existence of other related genes that are expressed in a tissue-specific manner. Since the Prdx6 transcripts exhibit differential regulation in response to growth and oxidative stress, further investigation may reveal their distinct roles in the cell and mechanism of regulation.
Alternative Transcript Putative Regulatory Element Polyadenylation Signal Sequence Prdx6 Expression Prdx6 Gene
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This research was supported by an ARA (Atorvastatin Research) Award to Shelley A. Phelan, sponsored by Pfizer Inc.
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