Investigación

Our primary research line focuses on the study of ribosome synthesis as they are responsible for protein synthesis and crucial elements in maintaining cell growth and proliferation. Functional ribosomes are constituted by two ribosomal subunits of different sizes present in a constant equilibrium in all living organisms. Ribosomal function and synthesis have been related to the development of many human diseases called ribosomopathies, but also in cancer, and age-related diseases.

The high conservation of ribosome synthesis in all eukaryotes allows the use of unicellular organisms as a model system. Among them, the baker yeast, Saccharomyces cerevisiae,  enormously facilitates the study of this complex process. Ribosomes are complex structures composed of at least 4 ribosomal RNAs and 78 ribosomal proteins. But more importantly, the synthesis of ribosomes consumes around 80% of all cellular resources in proliferating cells. Therefore, all processes involved are tightly coordinated.

Ribosome biogenesis starts with the synthesis of ribosomal RNA by the RNA polymerase I, which contains the RNA precursors of three out of the four ribosomal RNAs present in the functional ribosomes. Maturation of pre-ribosomes requires the action of more than 200 ribosome biogenesis factors participating in the synthesis, folding, and processing of the ribosomal RNA and the stable incorporation of ribosomal proteins.  In addition to RNA polymerase I, RNA polymerases II and III synthesize elements participating in ribosome biogenesis. While RNA polymerase III synthesizes the fourth ribosomal RNA present in the ribosomes, RNA polymerase II synthesizes several non-coding RNAs and the mRNAs encoding ribosomal proteins and ribosome biogenesis factors. Thus, ribosome biogenesis requires the coordinated action of RNA polymerases I, II, and III.

We think the constant balance between ribosomal subunits has been selected in evolution to avoid the influence of subunit amounts in selecting mRNAs to be translated. However, coordinating the balance between ribosomal subunits with the mRNAs to be translated might adapt the protein content to new cellular environments. Accordingly, impairing the balance between ribosomal subunits might be responsible for human diseases. Our work aims to characterize the molecular processes regulating the balanced expression of ribosomal subunits and the consequences of an imbalanced production on cell growth and protein homeostasis.