Seminar

Structural studies on the translational apparatus: a model system to understand and discover new strategy to control the cellular status

Paola Fucini, PhD

The healthy status of each organism, ranging from the simplest bacteria up to the most complex eukaryotic systems, including ourselves, is dependent on the ability of the cells to perform their basic physiological functions and respond to environmental or systematic signals in an appropriate and timely fashion. The protein content of the cell plays, in this respect, a determinant role as among all components of the cell, proteins take part in essentially each of its activities. Accordingly, the cellular proteome is maintained through a complex and intertwined regulation system and its disruption is linked to metabolic, oncogenic and neurodegenerative disorders. Of similar importance from the human prospective, small alterations in the proteome of the simplest organisms can lead to the transformation of symbiotic bacteria to pathogenic ones or mark the difference in the production of exquisite or dreadful food. The ribosome, resides at the core of the protein homeostasis network, not just because it is the macromolecular complex of the cell devoted to the synthesis of all its proteins, but also because it represents an ideal platform for the prompt intervention of a variety of factors that modulate the composition and architecture of either the ribosome or the newly synthesized polypeptide chain, de facto determining if and how the genetic information of the cell will be translated into its actual functional proteome. To further understand this fascinating and vital system, we have settled in our group to study at the structural level the ribosome in complex with its regulative factors as indeed, despite the extensive and still growing list of factors known to modulate the ribosome - reported in the range of thousands in human cells - for none of the existing mRNAs we know the identity of the specific elements that intervene in its translation and, for only very few of them, we have elucidated their mechanism of action. Among the vast repertoire of factors and mechanisms that regulate protein synthesis, in the last years we have focused our research on three main research lines, for which will be presented the latest results obtained and their possible exploitation to control the cellular status, namely the action of novel translational inhibitors and chaperones factors that intervene in ribosome biogenesis or the co-translational protein folding/sorting process.