Project description
Functional consequences of the defective ribosome biogenesis
Ribosome biogenesis is a complex process tightly coordinated with ribosomes' demand to ensure cellular growth. Ribosomes are generated in key steps where the ribosomal RNA is assembled with ribosomal proteins. Recently, the connection of defective ribosome biogenesis with human diseases has become clear. Mutations in ribosomal proteins, or biogenesis factors, increase the probabilities of cancer development. When a pre-ribosomal subunit suffers an assembly error, the particle is retained in the nucleus. Some aberrant pre-particles escape the surveillance mechanisms and are exported to the cytoplasm. The EU-funded RiboEscapers project aims to apply state-of-the-art ribosome profiling to study the functional consequences of ribosomal protein mutations, which generate defective ribosomes that are exported to the cytoplasm (RiboEscapers) and actively participate in translation.
Objective
Ribosomes are RNA-protein complexes found in all living cells. Ribosome biogenesis is a complex, cellular process that is tightly coordinated with ribosomes demand to ensure optimal cellular adaptation, growth and proliferation. In eukaryotes, ribosomes are sequentially generated in key steps where the ribosomal RNA (rRNA) is folded, modified, processed, and assembled with ribosomal proteins (r-proteins) to form the two ribosomal subunits. Recently, the connection of defective ribosome biogenesis with human diseases has become clear. This is the case of the so-called ribosomopathies, human syndromes caused by mutations in genes encoding either r-proteins or ribosome biogenesis factors, which are known to increase the probabilities of cancer development. Considering the multi-steps pathway of ribosome biogenesis, the possibilities to introduce errors with possible harmful effects for cell viability are high. In this context, cells have developed multiple surveillance mechanisms to supervise the structural and functional integrity of the ribosome particle. When a preribosomal subunit suffers an assembly error, in most of the cases, the aberrant particle is retained in the nucleus. However, some aberrant pre-particles have been shown to escape the surveillance mechanisms and to be exported to the cytoplasm.
This proposal, aims to explore the functional consequences of r-protein gene mutations, which generate defective ribosomal particles that are successfully exported to the cytoplasm (RiboEscapers) and actively participate in translation in yeast cell. For this purpose, the research action will combine traditional yeast tools together with state-of-the-art methodologies, such ribosome profiling to provide a detailed overview of the r-protein roles in ribosome biogenesis, as well as the consequences of specific defects in this process.
Fields of science
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
41004 Sevilla
Spain