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Research Paper|Volume 7, Issue 2|pp 133—143

Distinct regulation of Maf1 for lifespan extension by Protein kinase A and Sch9

Ying Cai1, Yue-Hua Wei1
  • 1No. 3 People's Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai 201900, China
Received: February 3, 2014Accepted: February 20, 2015Published: February 22, 2015
https://doi.org/10.18632/aging.100727

Copyright: © 2015 Cai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The Protein kinase A (PKA) and Sch9 regulates cell growth as well as lifespan in Saccharomyces cerevisiae. Maf1 is a RNA polymerase III (Pol III) inhibitor that tailors 5S rRNA and tRNA production in response to various environmental cues. Both PKA and Sch9 have been shown to phosphorylate Maf1 in vitro at similar amino acids, suggesting a redundancy in Maf1 regulation. However, here we find that activating PKA by bcy1 deletion cannot replace Sch9 for Maf1 phosphorylation and cytoplasmic retention; instead, such modulation lowers Maf1 protein levels. Consistently, loss of MAF1 or constitutive PKA activity reverses the stress resistance and the extended lifespan of sch9Δ cells. Overexpression of MAF1 partially rescues the extended lifespan of sch9Δ in bcy1Δsch9Δ mutant, suggesting that PKA suppresses sch9Δ longevity at least partly through Maf1 abundance. Constitutive PKA activity also reverses the reduced tRNA synthesis and slow growth of sch9Δ, which, however, is not attributed to Maf1 protein abundance. Therefore, regulation of lifespan and growth can be decoupled. Together, we reveal that lifespan regulation by PKA and Sch9 are mediated by Maf1 through distinct mechanisms