TOR and Proteasomal Regulation of Ribosomal Protein Gene Expression

Abstract

Previous studies have implicated SAGA (Spt-Ada-Gcn5-acetyltransferase) and TFIID (Transcription factor-IID) dependent mechanisms of transcriptional activation in yeast. SAGA-dependent transcriptional activation is further regulated by the 19S proteasome subcomplex. However, the role of the 19S proteasome subcomplex in transcriptional activation of the TFIID-dependent genes has not been elucidated. Ribosomal protein (RP) genes are important class of TFIID-dependent genes, and are crucial for ribosome biogenesis, protein synthesis, and hence cellular growth and proliferation. Since RP genes are TFIID-dependent and the role of the 19S proteasome subcomplex in their transcription remain unknown, we investigated whether 19S proteasome subcomplex regulates the transcription of RP genes. We find that the 19S proteasome subcomplex is recruited to the promoters of RP genes and enhances the targeting of co-activator NuA4 HAT (histone acetyl transferase) to activator Rap1. Such enhanced targeting of NuA4 HAT is essential to bring down TFIID complex in a HAT-dependent manner. Intriguingly, the HAT activity of NuA4 complex is regulated by environmental factors such as heat, nutrition and osmotic pressure via TOR (Target of Rapamycin) signaling pathway. We also find that TOR facilitates the targeting of 19S proteasome subcomplex to the promoters of RP genes to promote NuA4 HAT association, histone H4 acetylation and the formation of pre-initiation complex at their promoters. Together, our results delineate new regulatory pathway of RP gene expression via TOR, 19S proteasome subcomplex and NuA4 HAT.