Towards deciphering ribosome heterogeneity and polyribosome code to understand translational control of gene expression

Recently, ribosomes have been put in the spotlight as putative direct players in finely tuning translation by acting as mRNA filters. A handful of published papers suggests that ribosome composition is not fixed and uniform, but rather heterogeneous and modulated at the level of ribosomal proteins composition or rRNA variants and further modified post-translationally or post-transcriptionally. According to this idea, commonly regarded as “specialized ribosomes”, this ribosome heterogeneity could exert a direct role in mRNA selection or function. Specialized ribosomes could account for the long-standing debate about how tissue-specificity arise in ribosomopathies or other translation-related diseases, such as SMA . Additional ribosome-centered controls consider the importance of ribosome number and the existence of ribosome associated factors or RAFs which control translation efficiency. In this research line the lab aims at exploring this heterogeneity and understanding how it can impact the ultrastructural organization of polyribosomes. These complex macromolecular machinery are likely to display recurrent ribosome patterns and additional “epitranslational” changes which appeared during evolution and change during development. Using our unique transdisciplinary expertise ranging form biophysics to computational modelling and sequencing analysis, we aim at providing new models of polysomes and move towards a systemic and multi-dimensional view of translation.

Fund(s): 2019-2022 Telethon (Italy) The role of SMN protein in translation: implications for Spinal Muscular Atrophy (GV - Coordinator)

Members:
Mario Milani
Gabriella Viero (Principal investigator)