Yeast cells with vacuoles marked with Vph1-GF. Image credit: Henderson et al. 2014 (CC-BY 4.0)
In eukaryotic organisms such as yeast, the process of converting genes into proteins begins with the transcription of DNA sequences into mRNA molecules. An enzyme called RNA Polymerase II (Pol II) is responsible for creating new strands of mRNA, but a variety of other so called transcription factors is also needed to kickstart the transcription process. These transcription factors are delivered to genes, where they attach to specific sequences, or promoters, which sit at the beginning of each gene.
Once these transcription factors are in place, the double stranded DNA is unzipped to provide access to the DNA that will serve as the template for transcription. In budding yeast, Pol II and another specific transcription factor, known as TFIIH, work together to scan these promoter sequences to find the appropriate start sites of mRNA synthesis. However, several aspects of this process, such as how TFIIH works in promoter scanning, how far its scanning functions can extend, and how its activity is controlled, are currently poorly understood.
Zhao et al. have investigated these questions in budding yeast. Using a range of genetic and genomic techniques, Zhao et al. found that certain sections of TFIIH were involved in choosing specific transcription start sites of mRNA synthesis during promoter scanning. These sections were identical in different eukaryotic organisms from yeast to humans, suggesting that these regions may be important for tuning or controlling the activity of TFIIH. Moreover, in yeast, the activity of TFIIH determines how far the scanning unit was able to move along the promoter DNA.
Finally, Zhao et al. found that the initiation by promoter scanning was regulated by two distinct networks. The first network controlled how well mRNA synthesis could be initiated at individual transcription start sites; and the second network – driven by TFIIH – controlled which promoter sequences could be scanned to initiate transcription.
This research provides an in-depth look into the early steps of the process of converting DNA into mRNA. The biological machinery used to initiate and control this action is highly conserved between yeast and humans, suggesting that the mechanisms for controlling the activity of these factors could be similar, even if their initiation processes may differ.
