SMN-primed ribosomes modulate the translation of transcripts related to Spinal Muscular Atrophy

Fabio Lauria, Paolas Bernabò, Toma Tebaldi, Ewout Joan Nicholaas Groen, Elena Perenthaler, Federica Maniscalco, Annalisa Rossi, Deborah Donzel, Massimiliano Clamer, Marta Marchioretto, Neža Omersa, Julia Orri, Mauro Dalla Serra, Gregor Anderluh, Alessandro Quattrone, Alberto Inga, Thomas Henry Gillingwater, Gabriella Viero

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The contribution of ribosome heterogeneity and ribosome-associated proteins to the molecular control of proteomes in health and disease remains unclear. Here, we demonstrate that survival motor neuron (SMN) protein—the loss of which causes the neuromuscular disease spinal muscular atrophy (SMA)—binds to ribosomes and that this interaction is tissue-dependent. SMN-primed ribosomes are preferentially positioned within the first five codons of a set of mRNAs that are enriched for translational enhancer sequences in the 5′ untranslated region (UTR) and rare codons at the beginning of their coding sequence. These SMN-specific mRNAs are associated with neurogenesis, lipid metabolism, ubiquitination, chromatin regulation and translation. Loss of SMN induces ribosome depletion, especially at the beginning of the coding sequence of SMN-specific mRNAs, leading to impairment of proteins that are involved in motor neuron function and stability, including acetylcholinesterase. Thus, SMN plays a crucial role in the regulation of ribosome fluxes along mRNAs encoding proteins that are relevant to SMA pathogenesis.
Original languageEnglish
Pages (from-to)1239–1251
Number of pages13
JournalNature Cell Biology
Issue number10
Early online date21 Sept 2020
Publication statusPublished - 31 Oct 2020


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