SAGA and TFIID, general cofactors for RNA polymerase II transcription
Analysis of the newly synthesized mRNAs (right panel) shows that the inactivation of the SAGA complex in the budding yeast (spt20Δ) is accompanied by a decrease in the transcription of a vast majority of genes blue dots: 4982 genes showing a decrease of more than twice the levels of newly synthesized mRNAs in the spt20Δ strain with respect to the control strain). Analysis of total mRNAs (left panel) shows only very
Mol Cell Oct. 5, 2017
Sept. 17, 2017
The transcription of protein encoding genes is controlled by many multiprotein complexes: RNA polymerase II, general transcription factors, activators and transcriptional coactivators. While the majority of the coactivators seem to control the expression of sub-groups of genes, others play a global role in transcription. A study coordinated by Didier Devys in Làszlò Tora’s team at the IGBMC, in collaboration with researchers at the University of Seattle, shows that the SAGA complex acts as a general cofactor involved in the transcription of all genes and not only a subset of genes as suggested in previous studies. These results are published on 17 September 2017 in the journal Molecular Cell.
In addition to RNA polymerase II, the enzyme that catalyzes transcription of DNA into pre-messenger RNA, the expression of genes encoding proteins requires the involvement of many molecules: general transcription factors acting in concert with RNA polymerase II; activators that bind specific DNA sequences upstream of the genes and coactivators which are recruited by the activators and allow to "open" the chromatin to facilitate access of the transcriptional machinery to the DNA sequence. All the genes are therefore not transcribed at the same level, depending on the combination of activators and coactivators recruited from the regulatory sequences of these genes.
Previous studies in budding yeast suggested that 10% of the so-called "SAGA-dominated" genes required SAGA coactivator intervention to be transcribed while 90% of other so-called "TFIID-dominated" depended on the TFIDD coactivator. The use of new approaches to (i) map the location of SAGA throughout the genome, and (ii) quantify the mRNA synthesis, allowed the Làszlò Tora team at the IGBMC to re-evaluate the role of this coactivator in the transcript. In order to determine the involvement of the coactivators, the researchers usually analyzed the overall mRNA level in various yeast strains, resulting from the synthesis and degradation equilibrium of these mRNAs: this remained stable.
This time, the researchers chose to observe only the level of newly synthesized mRNAs which are a direct reflection of the activity of RNA polymerase II. They showed that this rate decreased significantly for all the genes analyzed and not only for the dependent SAGA genes. Another study, conducted in collaboration with researchers at the University of Seattle, on the TFIID complex, came to the same conclusion, showing that TFIID is necessary for the transcription of all genes by ANR polymerase II.
These results confirm, on the one hand, that an overall reduction in the synthesis of all the mRNAs results in an equivalent decrease in their degradation, thus maintaining a stable total rate and on the other hand demonstrating that SAGA and TFIID act as general cofactors for transcription by RNA polymerase II transcription, thus contradicting the previous classification.
This study was funded by the National Research Agency (ANR), the ARC Fundation, and the ERC.