RT Journal Article SR Electronic T1 In vivo translatome profiling reveals early defects in ribosome biology underlying SMA pathogenesis JF bioRxiv FD Cold Spring Harbor Laboratory SP 103481 DO 10.1101/103481 A1 Paola Bernabò A1 Toma Tebaldi A1 Ewout JN Groen A1 Fiona M Lane A1 Elena Perenthaler A1 Francesca Mattedi A1 Helen J Newbery A1 Haiyan Zhou A1 Paola Zuccotti A1 Valentina Potrich A1 Francesco Muntoni A1 Alessandro Quattrone A1 Thomas H Gillingwater A1 Gabriella Viero YR 2017 UL http://biorxiv.org/content/early/2017/01/26/103481.abstract 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.