Yeast Puf3p‐mediated mRNA decay is regulated by carbon source‐specific differential interaction of Puf3p with Pop2p and Yak1p

Puf3p regulates the stability of nuclear‐encoded mRNAs acting in mitochondrial biogenesis and function in Saccharomyces cerevisiae. This work identifies the phosphorylation of Pop2p, a component of the deadenylase complex, as being critical for adapting Puf3p‐mediated mRNA decay upon carbon source alterations. We demonstrate that the Puf3p–Pop2p association diminishes in mitochondria‐reliant conditions and establish Yak1p, a kinase that phosphorylates Pop2p at threonine 97, as a new player in Puf3p‐mediated regulation of mRNA decay. Yak1p deletion alters the half‐life of Puf3p target mRNAs. Our findings outline a metabolism‐driven regulatory switch, whereby, in mitochondria‐independent conditions, Puf3p recruits Pop2p and the decay machinery to bound mRNAs for rapid decay. Conversely, in mitochondria‐reliant conditions, the association of Puf3p with Yak1p increases, placing Yak1p proximal to neighboring Pop2p. Subsequent Pop2p phosphorylation reduces the Puf3p–Pop2p interaction and stabilizes Puf3p target mRNAs. Puf3p regulates the stability of nuclear‐encoded mRNAs that code for proteins involved in mitochondrial biogenesis and function. Our findings outline a metabolism‐driven regulatory switch, whereby, in mitochondria‐independent (dextrose) conditions, Puf3p recruits Pop2p of the deadenylase complex and the decay machinery to mRNAs for rapid decay. Conversely, in mitochondria‐reliant (galactose) conditions, the association of Puf3p with the kinase Yak1p increases, placing Yak1p proximal to Pop2p. Subsequent Pop2p phosphorylation by Yak1p reduces the Puf3p–Pop2p interaction for mRNA stabilization.