| First Author | Lauria F | Year | 2020 |
| Journal | Nat Cell Biol | Volume | 22 |
| Issue | 10 | Pages | 1239-1251 |
| PubMed ID | 32958857 | Mgi Jnum | J:313368 |
| Mgi Id | MGI:6709603 | Doi | 10.1038/s41556-020-00577-7 |
| Citation | Lauria F, et al. (2020) SMN-primed ribosomes modulate the translation of transcripts related to spinal muscular atrophy. Nat Cell Biol 22(10):1239-1251 |
| abstractText | 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. |
