Telomere maintenance by intracellular signals: New kid on the block?

Abstract

The pervasive inositol phosphate signaling family includes a specialized subgroup with “high-energy” pyrophosphate groups that turn over rapidly (Fig. 1 and refs. 1 and 2). Some of the enzymes directing these reactions have yet to be cloned (see Fig. 1 legend). Therefore, proposed roles of inositol pyrophosphates ([PP]x-IPy) in vivo have inevitably depended on observing phenotypes when the entire subgroup is either eliminated or overproduced. Such experiments have led to conclusions that inositol pyrophosphates act as a group to regulate apoptosis, vesicle trafficking, yeast vacuole biogenesis, transcription, chemotaxis, and DNA repair (see ref. 3 for access to the literature). This tendency to treat these pyrophosphates as all acting in a functionally similar manner has not helped us understand the molecular basis by which they apparently regulate so many biological processes. Now, two groups working independently [Sol Snyder's laboratory at Johns Hopkins as described in this issue of PNAS (4) and John York's team at Duke (5)] have used yeast genetics to obtain evidence that inositol pyrophosphates regulate yet another fundamental process, in this case telomere length. However, an important new feature of these studies is that specific inositol pyrophosphates, namely, those with a hydroxyl group at the 2-position (Fig. 1), are held responsible for this biological activity. This departure from the standpoint that inositol pyrophosphates are a functionally redundant family offers opportunities to develop a molecular understanding of these specific events.