AFM Telethon - RiboSMA Viero (DFM.AD004.312)

Area tematica

Scienze fisiche e tecnologie della materia

Area progettuale

Struttura responsabile del progetto di ricerca

Istituto di biofisica (IBF)

Responsabile di progetto

GABRIELLA VIERO
Telefono: 0461-314033
E-mail: viero.gabriella@cnr.it

Abstract

Spinal Muscular Atrophy is an autosomal recessive disease caused by mutations in the survival motor neuron (SMN) protein. Current SMNrestoration therapies remain only partially effective for many patients and therefore do not represent a definitive 'cure'. Only by understanding the full spectrum of SMN's functions will we be able to develop more effective, second-generation, therapeutic options. Although SMN is classically known to have housekeeping roles in RNP biogenesis, this function cannot recapitulate SMA pathogenesis or motor neuron susceptibility. Using our unique toolbox of comparative and integrative approaches we showed that, in addition to its canonical roles, SMN protein is a ribosome modulator, binding to a subset of ribosomes that we termed "SMN-primed" ribosomes. SMN loss leads not just to global translational defects in vivo and in cellulo, but also to early and local dysfunction of ribosome fluxes along several mRNAs in disease-relevant tissues. The overarching objective is to demonstrate that the functional role of SMN in translation is pivotal to the comprehensive molecular mechanisms of SMA pathogenesis. Building on these fundamentals of SMN biology, we then ai

Data inizio attività

18/09/2021

Parole chiave

ribosome, protein, therapies SMA

Ultimo aggiornamento: 13/12/2024