PT - JOURNAL ARTICLE AU - Paola Bernabò AU - Toma Tebaldi AU - Ewout JN Groen AU - Fiona M Lane AU - Elena Perenthaler AU - Francesca Mattedi AU - Helen J Newbery AU - Haiyan Zhou AU - Paola Zuccotti AU - Valentina Potrich AU - Francesco Muntoni AU - Alessandro Quattrone AU - Thomas H Gillingwater AU - Gabriella Viero TI - <em>In vivo</em> translatome profiling reveals early defects in ribosome biology underlying SMA pathogenesis AID - 10.1101/103481 DP - 2017 Jan 01 TA - bioRxiv PG - 103481 4099 - http://biorxiv.org/content/early/2017/01/26/103481.short 4100 - http://biorxiv.org/content/early/2017/01/26/103481.full AB - Background Genetic alterations impacting on ubiquitously expressed proteins involved in mRNA metabolism often result in neurodegenerative conditions, with increasing evidence suggesting that translational defects can contribute to disease. Spinal Muscular Atrophy (SMA) is a neuromuscular disease caused by low levels of SMN protein, whose role in disease pathogenesis remains unclear.Results By determining in parallel the in vivo transcriptome and translatome in SMA mice we identified a robust decrease in translational efficiency, arising during early stages of disease. Translational defects affected translation-related transcripts, were cell autonomous, and were fully rescued after treatment with antisense oligonucleotides to restore SMN levels. Defects in translation were accompanied by a decrease in the number of ribosomes in motor neurons in vivo.Conclusion Our findings suggest that neuronal tissues and cells are particularly sensitive to perturbations in translation during SMA, and identify ribosome biology as an important, yet largely neglected, factor in motor neuron degeneration.