In vivo translatome profiling in spinal muscular atrophy reveals a role for SMN protein in ribosome biology

Paola Bernabò, Toma Tebaldi, Ewout J.N. Groen, Fiona M. Lane, Elena Perenthaler, Francesca Mattedi, Helen J. Newbery, Haiyan Zhou, Paola Zuccotti, Valentina Potrich, Hannah K. Shorrock, Francesco Muntoni, Alessandro Quattrone, Thomas H. Gillingwater, Gabriella Viero

Research output: Contribution to journalArticlepeer-review


Genetic alterations impacting ubiquitously expressed proteins involved in RNA metabolism often result in neurodegenerative conditions, with increasing evidence suggesting that translation defects can contribute to disease. Spinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of SMN protein, whose role in pathogenesis remains unclear. Here, we identified in vivo and in vitro translation defects that are cell autonomous and SMN dependent. By determining in parallel the in vivo transcriptome and translatome in SMA mice, we observed a robust decrease in translation efficiency arising during early stages of disease. We provide a catalogue of RNAs with altered translation efficiency, identifying ribosome biology and translation as central processes affected by SMN depletion. This was further supported by a decrease in the number of ribosomes in SMA motor neurons in vivo. Overall, our findings suggest ribosome biology as an important, yet largely overlooked, factor in motor neuron degeneration.
Original languageEnglish
Pages (from-to)953–965
Number of pages13
JournalCell Reports
Issue number4
Early online date26 Oct 2017
Publication statusE-pub ahead of print - 26 Oct 2017

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