In yeast, transcription of ribosomal DNA (rDNA) by RNA polymerase I (Pol We) is regulated by unique mechanisms performing at the amount of the enzyme. wild-type stress, suggesting that Pol I dimerization downregulates rDNA transcription. Furthermore, it had been also proven that Pol II or Pol III usually do not homodimerize under nutrient starvation, indicating that setting of transcriptional inactivation is exclusive for Pol I. Pol I dimerization is seen as a hibernating system under severe environmental conditions (Amount?2). Pol I hibernation might protect the enzyme from degradation and, simultaneously, enable fast reactivation when favourable growth conditions are restored. Hyal1 Interestingly, a similar mode of hibernation by dimerization offers been observed for bacterial ribosomes [34,35]. Nevertheless, while the formation of ribosome homodimers, also termed disomes, relies on external factors that bind prior to dimerization, structural studies founded that Pol I dimerization does not require binding of external factors [19,20]. Moreover, it was demonstrated that Rrn3 addition is unable to disassemble Pol I dimers [23]. Consequently, control of the Pol I monomer-dimer transition relies on yet undescribed regulatory mechanisms. In addition to dimerization, hibernation implies cleft expansion and purchasing of the DNA-mimicking loop inside the cleft. In Pol II and bacterial RNA polymerase, it was shown that certain RNAs and proteins can block the enzyme by binding inside the cleft [36C38]. The DNA-mimicking loop within the expander could possess a safety function in the Pol I hibernating state, by hampering the binding of macromolecules that could compromise enzyme reactivation. The part of phosphorylation Phosphorylation might perform an important part in Pol I activation and inactivation. It was shown that only unphosphorylated Rrn3 will be able to bind Pol I in yeast, while the polymerase must be phosphorylated for this interaction to occur [39]. In agreement, the S145D phospho-mimetic mutation BMS-650032 tyrosianse inhibitor in yeast Rrn3 impairs the formation of the Pol I-Rrn3 complex and associates with reduced levels of both Pol I and Rrn3 on rDNA promoters [40]. In addition, a proteomic study in yeast exposed a number of phosphosites in Pol I-specific subunits A190, A34.5 and A43, but single mutations of specific residues did not impact Pol I-Rrn3 complex formation [41]. However, all A43 phosphosites recognized in this statement locate in regions connected with Pol I dimerization. In particular, Ser208 and Ser220 lie next to the Pol I dimer interface, while Ser262/263 and Ser285 belong to the A43 C-terminal tail, which is essential for dimerization. This suggests that, rather than a direct effect on Rrn3 interaction, phosphorylation of the A43 C-terminal region may regulate the Pol I monomer-dimer transition. Interestingly, Ser220 and Ser262/263 are fully exposed in the dimeric configuration, while Ser208 is definitely in a flexible BMS-650032 tyrosianse inhibitor loop [19,20]. Consequently, phosphorylation of these residues may travel dimer disassembly, while Ser285 may play a role at a later on stage. In a scenario of nutrient deprivation, dephosphorylation of the A43 C-terminal region would allow dimer formation (Number?2). When nutrients are restored, phosphorylation of this region in Pol I dimers would increase the levels of free monomeric Pol I, while dephosphorylation of Rrn3 would allow the formation of Pol I-Rrn3 complexes to restore rDNA transcription. Identification of the kinases and phosphatases controlling this process will likely provide clues to understand how this transcription system is definitely regulated. Finally, phosphorylation may also play a role in the regulatory function of the expander. Ser1413, Ser1415 and Ser1417 in subunit A190, all belonging to this loop, were identified as phosphosites in the proteomic study [41]. Deletion of the DNA-mimicking loop within the expander exhibits a moderate growth phenotype at 37 oC [20] but the phosphosites lie outside the BMS-650032 tyrosianse inhibitor deleted.