Versatile Galactose Genetic Switch

In eucaryotes, three distinct species of RNA polymerases (RNA Pol) have been identified while prokaryotes and archaea have only one RNA polymerase. In eukaryotes, RNA PolI, transcribes the large rRNA precursor that is processed leading to the production of 28 S, 18 S and 5.8 S rRNAs. RNA PolII, transcribes heterogeneous nuclear RNAs (hnRNAs) and small nuclear RNAs (sn RNAS). hnRNAs are processed to mature mRNA, which requires snRNAs. RNA PolIII transcribes 5 S rRNA and tRNAs. The identity of these three RNA polymerases has been confirmed by molecular genetic and biochemical analysis. Although these enzymes share a common property of transcribing DNA, they lack the ability to identify the transcription initiation sites for which they depend on additional proteins. As expected, the promoters of genes transcribed by these RNA polymerases also have unique features.

Of the three polymerases, PolII has attracted considerable attention owing to the fact that its activity is highly regulated. The fundamental question is: How does the transcriptional machinery direct the RNA PolII to accurately transcribe the diverse set of genes depending upon the physiological need? In general, promoters served by the RNA PolII have a common architecture consisting of core elements required for the promoter function and for the assembly and orientation of the pre-initiation complex. The most significant structural elements are the TATA sequences located 25 nucleotides upstream of the transcription initiation site. The transcription initiation site is generally pyrimidine-rich. In addition, the promoters contain regulatory sequences that govern the expression status by interacting with specific transcriptional regulators. GAL promoter is an archetypical PolII promoter that is turned OFF by glucose and ON by galactose. We shall focus on how Gal4p, the DNA-binding transcriptional activator, activates PolII to transcribe GAL genes in response to the inducer.