The 'scavenger' m7GpppX pyrophosphatase activity of Dcs1 modulates nutrient-induced responses in yeast.
Dcs1, the m7GpppX pyrophosphatase of Saccharomyces cerevisiae, has been reported to 'scavenge' capped 5' end fragments generated by 3'-->5' mRNA degradation. We now show that the absence of Dcs1, and the closely related Dcs2 protein, compromises cellular responses to glucose-deprivation stress as well as to step changes in glucose availability. Dcs1 and Dcs2 form homo- and heterodimers, with the heterodimer appearing as cells enter diauxie. Despite the previously observed increase in abundance of the mRNA encoding the neutral trehalase (Nth1) in the stationary phase, the total enzyme activity of Nth1 decreases in this phase of growth. Changes in trehalase activity are significant because the non-reducing disaccharide trehalose is thought to stabilize cellular components under stress conditions. In the dcs1Delta and dcs1Deltadcs2Delta mutants, normal regulation of trehalase activity is lost. Nutrient stress induces DCS1 and DCS2 transcription via the cAMP-PKA signalling pathway. Dcs1 also becomes phosphorylated as the availability of glucose diminishes, and we test the role of this phosphorylation in the stress response. Further evidence indicates that Dcs1 plays a complementary role to the translation factor eIF4E in preventing capped 5' fragments of mRNA from interfering with translation initiation. We conclude that Dcs1 function influences cellular responses to changes in nutrient avialability, while Dcs2 seems to act as a modulator of Dcs1 function.
Malys
Naglis
N
Posttranscriptional Control Group, Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology, Manchester M60 1QD, UK.
Carroll
Kathleen
K
Miyan
Jaleel
J
Tollervey
David
D
McCarthy
John E G
JE
D048868:Adaptor Proteins, Signal Transducing; D001483:Base Sequence; D003470:Culture Media; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D019281:Dimerization; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D008969:Molecular Sequence Data; D009699:N-Glycosyl Hydrolases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D011755:Pyrophosphatases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014198:Trehalase / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D003470:Culture Media; C487769:Dcs2 protein, S cerevisiae; D039561:Eukaryotic Initiation Factor-4E; D010750:Phosphoproteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D014198:Trehalase; C478395:DCS1 protein, S cerevisiae; D009699:N-Glycosyl Hydrolases; D011755:Pyrophosphatases; C021798:5'-(N(7)-methyl 5'-triphosphoguanosine)-(mRNA) diphosphatase