SMN-primed ribosomes modulate the translation of transcripts related to spinal muscular atrophy
Open accessPublished version of a preprint
Abstract
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.
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References 83 · Cited by 98
- Authors
- Lauria, F., Bernabò, P., Tebaldi, T., Groen, E. J. N., Perenthaler, E., Maniscalco, F., Rossi, A., Donzel, D., Clamer, M., Marchioretto, M., Omersa, N., Orri, J., Dalla Serra, M., Anderluh, G., Quattrone, A., Inga, A., Gillingwater, T. H., & Viero, G.
- Affiliations
- National Research Council (IT)
- University of Trento (IT)
- University Medical Center Utrecht (NL)
- Erasmus MC (NL)
- National Institute of Chemistry (SI)
- Fundació Jesuïtes Educació (ES)
- Euan MacDonald Centre for Motor Neuron Disease Research (GB)
- Corresponding author
- Viero, Gabriella
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2020-09-21
- Volume
- 22
- Issue
- 10
- Pages
- 1239-1251
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC7610479
- OpenAlex
- W3087754470
- Cited by
- 98
- References
- 83
- Citations by year
- 2026: 8 · 2025: 20 · 2024: 20 · 2023: 16 · 2022: 19 · 2021: 13 · 2020: 2
- FWCI
- 4.06
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Nature Cell Biology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Institutional Research Information System (Università degli Studi di Trento) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- Fondazione Cassa Di Risparmio Di Trento E Rovereto (young Post-doc funding grant)
- European Cooperation in Science and Technology (CA15126)
- Javna Agencija za Raziskovalno Dejavnost RS (P1-0391)
- Wellcome Trust (106098/Z/14/Z)
- Provincia Autonoma di Trento (AxonomiX)
- AFM-Téléthon (22129)
- Fondazione Telethon (GGP19115)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- survival motor neuron protein, spinal muscular atrophy, ribosome heterogeneity, ribosome-associated proteins, translational regulation, 5' untranslated region, rare codons, translational enhancer, acetylcholinesterase, motor neuron function
- MeSH terms
- Animals, Disease Models, Animal, Gene Expression Regulation, Motor Neurons, Muscular Atrophy, Spinal, Ribosomes, RNA, Messenger, Protein Biosynthesis, Proteome, Mice, Survival of Motor Neuron 1 Protein, Transcriptome
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