PMT1 deficiency enhances basal UPR activity and extends replicative lifespan of Saccharomyces cerevisiae
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Pmt1p is an important member of the protein O-mannosyltransferase (PMT) family of enzymes, which participates in the endoplasmic reticulum (ER) unfolded protein response (UPR), an important pathway for alleviating ER stress. ER stress and the UPR have been implicated in aging and age-related diseases in several organisms; however, a possible role for PMT1 in determining lifespan has not been previously described. In this study, we report that deletion of PMT1 increases replicative lifespan (RLS) in the budding yeast Saccharomyces cerevisiae, while overexpression of PMT1 (PMT1-OX) reduces RLS. Relative to wild-type and PMT1-OX strains, the pmt1Δ strain had enhanced HAC1 mRNA splicing and elevated expression levels of UPR target genes. Furthermore, the increased RLS of the pmt1Δ strain could be completely abolished by deletion of either IRE1 or HAC1, two upstream modulators of the UPR. The double deletion strains pmt1Δhac1Δ and pmt1Δire1Δ also displayed generally reduced transcription of UPR target genes. Collectively, our results suggest that PMT1 deficiency enhances basal activity of the ER UPR and extends the RLS of yeast mother cells through a mechanism that requires both IRE1 and HAC1.
KeywordsProtein O-mannosyltransferase Lifespan Unfolded protein response Saccharomyces cerevisiae
This work was supported by grants from the National Natural Science Foundation of China (31101051, 81170327), the Natural Science Foundation of Guangdong Province (9252402301000002), the Science & Technology Innovation Fund of Guangdong Medical College (STIF201102), and the Natural Science on the Surface of Guangdong Medical College (XK1204). This work was also supported by NIH Grant R01AG039390 to MK. MM was supported by NIH training grant T32AG000266. BMW was supported by NIH training grant T32 ES007032.
Conflict of interest
None of the authors has any conflict of interests that could affect the performance of the work or the interpretation of the data.
- Kaeberlein M, Kennedy BK (2005) Large-scale identification in yeast of conserved ageing genes. Mech Ageing Dev (1) 17–21. doi: 10.1016/j.mad.2004.09.013
- Mori T, Ogasawara C, Inada T et al (2010) Dual functions of yeast tRNA ligase in the unfolded protein response: unconventional cytoplasmic splicing of HAC1 pre-mRNA is not sufficient to release translational attenuation. Mol Biol Cell 21(21):3722–3734. doi: 10.1091/mbc.E10-08-0693 PubMedCentralPubMedCrossRefGoogle Scholar
- Steffen KK, Kennedy BK, Kaeberlein M (2009) Measuring replicative life span in the budding yeast. J Vis Exp (28). doi: 10.3791/1209 1209