The formation of ribosomes in proliferating cells. Alterations in cancer and ribosomopathies

Ponente: Blanca Nieto Bernáldez

Centro de Investigación del Cáncer (CIC-IBMCC), laboratorio 3

Host: -

Fecha: 16/02/2017

Hora: 12:30

Salón de Actos del Centro de Investigación del Cáncer

Ribosome synthesis takes place within the most prominent nuclear substructure, the nucleolus. It is a multistep process that entails pre-rRNA transcription, pre-rRNA processing, and assembly of ribosomal proteins imported from the cytoplasm. These activities require the participation of more than 200 trans-acting factors. The majority of studies on ribosome formation have been performed in yeast, and it has long been assumed that most features are similar in humans. However, although the basic aspects are conserved, there are many maturation events, and links to other processes, that are unique of higher eukaryotes. One such link is the nucleolar stress response, which is mediated by p53 and is triggered by defects in ribosome synthesis. This response is receiving intense attention because it is the cause of various human diseases known as ribosomopathies. In the cancer field, recent studies have shown that up-regulation of ribosome synthesis might serve as a driving force in malignancy. Despite the growing interest, progress in understanding ribosome synthesis in humans is greatly hampered by technical limitations. Powerful approaches used in yeast, such as genetic screens to identify trans-acting factors or purification of pre-ribosomes by tandem-affinity chromatography, are not possible in human cells. In our laboratory we have optimized a series of techniques to monitor the formation of several pre-ribosomal complexes in human cells. We are studying normally-growing cells and cells blocked at specific steps of ribosome maturation. Data will be shown on the defects in ribosome synthesis that occur in Diamond-Blackfan anemia and on the effects of ribosome export inhibitors used in cancer therapy.