PaGrg1, a glucose-repressible gene of Podospora anserina that is differentially expressed during lifespan

A loss-of-function mutation in Grisea, a gene of Podospora anserina that was previously shown to code for a copper-modulated transcription factor, leads to a significant increase in lifespan. In an attempt to identify and to isolate potential target genes controlled by GRISEA, a RT-differential-display screen was performed. This approach resulted in the identification of a gene, PaGrg1, that is differentially expressed in the wild-type and in the long-lived grisea mutant. In the mutant, transcript levels of PaGrg1 were found to be much lower than in the wild-type even if copper was added to the growth medium in amounts that revert the phenotype of this copper-uptake mutant to wild-type characteristics. PaGrg1 is a discontinuous gene with a single intron and encodes a protein of 71 amino acids sharing a high degree of sequence identity (65%) with the developmentally regulated, catabolite-repressed grg-1 gene of Neurospora crassa. Transcription of PaGrg1 increases upon carbon starvation indicating that PaGRG1 represents a putative stress protein. Transcript levels of PaGrg1 were found to increase during aging in both the wild-type strain and the long-lived mutant. However, even in the senescent stage of grisea, they are much lower than in juvenile cultures of the wild-type strain. The data suggest that threshold transcript levels of PaGPg1, and/or additional unidentified genes which are controlled by GRISEA and which are subject to catabolite repression, are significantly involved in lifespan control. This conclusion is supported by the finding that, in contrast to the wildtype, the lifespan of grisea does not increase when cultures are grown on non-repressible carbon sources.