Inositol pyrophosphates regulate RNA polymerase I-mediated rRNA transcription in Saccharomyces cerevisiae

We examined whether inositol pyrophosphates, energy-rich derivatives of inositol which act as metabolic messengers, play a role in ribosome synthesis in the budding yeast, Saccharomyces cerevisiae. Yeast lacking the IP6 kinase Kcs1, which is required for the synthesis of inositol pyrophosphates, display increased sensitivity to translation inhibitors and decreased protein synthesis. These phenotypes are reversed upon the expression of enzymatically active Kcs1, but not the inactive form. kcs1Δ yeast exhibit reduced levels of ribosome subunits, suggesting that they are defective in ribosome biogenesis. The rate of rRNA synthesis, the first step of ribosome biogenesis, is decreased in kcs1Δ yeast, suggesting that RNA polymerase I (Pol I) activity may be reduced in these cells. We determined that the Pol I subunits, A190, A43 and A34.5 can accept a β phosphate moiety from inositol pyrophosphates to undergo serine pyrophosphorylation. Although there is impaired rRNA synthesis in kcs1Δ yeast, we did not find any defect in recruitment of Pol I on rDNA, but observe that the rate of transcription elongation is compromised. Taken together, our findings highlight inositol pyrophosphates as novel regulators of rRNA transcription.

Source: BJ Gene - November 24, 2014 Category: Biochemistry Authors: S Gowri Thota, C Unnikannan, S R. Thampatty, R Manorama, R Bhandari Tags: BJ Signal Source Type: research