**7. Conclusions**

*Gene Expression and Control*

**Figure 2.**

summarized in **Figure 2**.

*Saccharomyces cerevisiae*.

regulation of RPGs and rRNAs [56].

**6. The TCT-motif module in metazoan RPG**

essential for accurate translation activity. The coordinated regulation and expression of the RPG with other ribosomal components is still poorly understood. However, in the fission yeast *Schizosaccharomyces pombe*, it is known that rRNAs, RPGs, and box C/D snoRNAs contain in their promoters a HomolD-box [39, 53], which might be able to control the expression of those genes. Moreover, the Rrn7 transcription factor, which is the HomolD-box-binding protein in RPG, was found to be responsible for the control of the gene expression of box C/D snoRNAs and RPGs *in vivo* in *Schizosaccharomyces pombe* cells [53]. Interestingly, the yeast orthologs of the human RECQL/DDB1 complex may recognize the HomolD-box and down-regulate RPG expression [53]. Taking all these results together, we propose a model, in which the HomolD-box is bound by Rrn7 and co-regulates the transcription of RPG, box C/D snoRNA and rRNA genes in the fission yeast. This model is

*promoters contain a HomolD-box, which is critical for in vivo transcription.*

Role of HomolD-box-containing promoters in ribosome biogenesis**.** *It is believed that the coordinated expression of genes that encode ribosome components (rRNA, RPG, box C/D snoRNA) is due to a common DNA element (HomolD-box) that is able to bind a protein factor (Rrn7). The presence of the HomolD-box in the promoters of several genes encoding ribosome components indicates a common regulation. Until now, experiments have demonstrated that Rrn7 binds to rRNA and RPG promoters in Schizosaccharomyces pombe. However, binding of Rrn7 to box C/D snoRNA promoters has not been demonstrated yet, although those* 

Unlike *Schizosaccharomyces pombe* in the case of *Saccharomyces cerevisiae*, there is accumulated evidence that show a putative coordinated model to regulate biogenesis of ribosome components. In this model, CK2 protein kinase is part of protein complexes that regulate RPG expression and rRNA synthesis [54] and interact with the protein Fhl1p that is associated to Ifh1p, which binds to the IFH1 element near to the Rap1 sequence. CK2 and Ifh1p are part of the complex CURI associated to rRNA processing and RPG transcription [55]. Also, in *S. cerevisiae,* another protein has been identified and named protein HmoI, which is associated with the transcription

In addition to the role of CK2 to modulate Rrn7 function in *Schizosaccharomyces pombe* during HomolD-box directed transcription, there might be another points of regulation related to protein complexes, such as those described in the yeast

The analyses of insect and mammalian RPG promoters have shown the presence of a common core promoter element that is part of the poly-pyrimidine initiator (TCT)-motif family, which is a novel core promoter element necessary to initiate transcription in those genes [35, 57]. In these promoters, the transcription start site (TSS) involves the TCT motif and is positioned around −2 to +6 relative to TSS, competing with exactly the same position as the Inr. However, the features of

**158**

The fission yeast *Schizosaccharomyces pombe* provides an excellent biological model to study the coordinated expression of ribosome components. The finding that rDNAs, RPGs, and box C/D snoRNAs genes contain a HomolD-box, which is most likely bound by Rrn7, provides the starting point to investigate this issue. The most important questions to answer are: (i) to determine whether or not box C/D snoRNA genes are transcribed by the same transcription apparatus that transcribes RPG; (ii) to identify the signal that activates transcription of HomolD-box containing genes, and (iii) to identify the HomolE-binding protein. The resolution of all these issues would contribute to understand the regulation of RPG transcription in the fission yeast and most likely could be extrapolated to metazoan organisms.

## **Acknowledgements**

This work has been funded by the Corporación Nacional de Ciencia y Tecnología de Chile (CONICYT), Fondo de Desarrollo de Ciencia y Tecnología (FONDECYT), and FONDEF (ID16I10145). We are very grateful to Mrs. Teresa Donoso for her continued support to F. U. and E. M.
