The SMN-ribosome interplay: a new opportunity for Spinal Muscular Atrophy therapies

The underlying cause of Spinal Muscular Atrophy (SMA) is in thereduction of survival motor neuron (SMN) protein levels due to mutationsin the SMN1 gene. The specific effects of SMN protein loss and theresulting pathological alterations are not fully understood. Given thecrucial roles of the SMN protein in snRNP biogenesis and itsinteractions with ribosomes and translation-related proteins and mRNAs,a decrease in SMN levels below a specific threshold in SMA is expectedto affect translational control of gene expression. This review coversboth direct and indirect SMN interactions across varioustranslation-related cellular compartments and processes, spanning fromribosome biogenesis to local translation and beyond. Additionally, itaims to outline deficiencies and alterations in translation observed inSMA models and patients, while also discussing the implications of therelationship between SMN protein and the translation machinery withinthe context of current and future therapies.