Maf1 and the integration of signaling pathways mediating transcriptional repression by RNA polymerase III.
JaeHoon Lee, Neelam Desai, Rajendra Upadhya, Ian Willis
Department of Biochemistry, Albert Einstein Col. Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA
The transcription of ribosomal components and tRNAs accounts for more than 80% of nuclear gene transcription, involves all three nuclear RNA polymerases (pols) and is rapidly and coordinately repressed under conditions that are deleterious for cell growth. An important unresolved question is whether the diverse pathways that signal unfavorable growth conditions and repress ribosome and tRNA synthesis function in parallel or converge. In the case of pol III transcription, convergent signaling pathways are indicated by studies on Maf1, an essential pol III-specific mediator of repression. Strains deleted for MAF1 are blocked in the repression of pol III transcription under all conditions that have been tested to date. These include secretory defects, nutrient starvation, growth to stationary phase, DNA damage, ER and oxidative stress and various drug treatments. The mechanisms and targets of Maf1-dependent transcriptional repression have been examined in vivo and in vitro using the antifungal compound, chlorpromazine to induce repression. Two steps in pol III transcription are inhibited in a Maf1-dependent manner: De novo assembly of the initiation factor TFIIIB by TFIIIC and the recruitment of pol III to pre-assembled TFIIIB-DNA complexes. The inhibition of both of these steps has been recapitulated in vitro using recombinant Maf1 and provides insight into the function of this novel protein.
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