Dcs2, a Novel Stress-induced Modulator of m7GpppX Pyrophosphatase Activity that Locates to P Bodies

The eukaryotic “scavenger” type decapping enzyme, an m7GpppX pyrophosphatase, is active in cellular mRNA metabolism and thereby influences posttranscriptional gene expression. The yeast version of this enzyme, Dcs1, catalyses cleavage of 5′end m7G-oligoribonucleotide fragments generated by 3′→5′ exonucleolytic decay, and cleavage of m7GDP generated by Dcp1/Dcp2-mediated decapping in the 5′→3′ decay pathway. We show that Dcs1 is active as a homodimer with low KM values for cleavage of m7GpppG (0.14 μM) and m7GDP (0.26 μM). Previous work showed that the paralogous DCS2 gene is transcriptionally induced via the amp-PKA pathway as yeast enters diauxie. The resulting Dcs2 protein forms a heterodimer together with Dcs1, both modulating Dcs1 substrate specificity and suppressing its kcat. Since Dcs2 is recruited into cytoplasmic P bodies, its inhibitory function may be focused in these centres of mRNA storage/turnover. Dcs2 is therefore a novel type of stress-induced regulatory protein that modulates m7GpppX pyrophosphatase activity. Moreover, inhibition of Dcs1 activity by Dcs2, like depletion of Dcs1, reduces chronological life span, possibly by modulating m7G misincorporation into nucleic acids. This could potentially link control of mRNA metabolism with senescence.