Academic Journal
Premature termination codons in SOD1 causing Amyotrophic Lateral Sclerosis are predicted to escape the nonsense-mediated mRNA decay
| العنوان: | Premature termination codons in SOD1 causing Amyotrophic Lateral Sclerosis are predicted to escape the nonsense-mediated mRNA decay |
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| المؤلفون: | Guissart, Claire, Mouzat, Kevin, Kantar, Jovana, Louveau, Baptiste, Vilquin, Paul, Polge, Anne, Raoul, Cédric, Lumbroso, Serge |
| المساهمون: | Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire de Biochimie CHRU Nîmes, Hopital Saint-Louis AP-HP (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) |
| المصدر: | ISSN: 2045-2322. |
| بيانات النشر: | HAL CCSD Nature Publishing Group |
| سنة النشر: | 2020 |
| المجموعة: | Université de Montpellier: HAL |
| مصطلحات موضوعية: | [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; Amyotrophic lateral sclerosis (ALS) is the most common and severe adult-onset motoneuron disease and has currently no effective therapy. Approximately 20% of familial ALS cases are caused by dominantly-inherited mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1), which represents one of the most frequent genetic cause of ALS. Despite the overwhelming majority of ALS-causing missense mutations in SOD1, a minority of premature termination codons (PTCs) have been identified. mRNA harboring PTCs are known to be rapidly degraded by nonsense-mediated mRNA decay (NMD), which limits the production of truncated proteins. The rules of NMD surveillance varying with PTC location in mRNA, we analyzed the localization of PTCs in SOD1 mRNA to evaluate whether or not those PTCs can be triggered to degradation by the NMD pathway. Our study shows that all pathogenic PTCs described in SOD1 so far can theoretically escape the NMD, resulting in the production of truncated protein. This finding supports the hypothesis that haploinsufficiency is not an underlying mechanism of SOD1 mutant-associated ALS and suggests that PTCs found in the regions that trigger NMD are not pathogenic. Such a consideration is particularly important since the availability of SOD1 antisense strategies, in view of variant treatment assignment. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/33244158; PUBMED: 33244158; PUBMEDCENTRAL: PMC7691510 |
| DOI: | 10.1038/s41598-020-77716-5 |
| الاتاحة: | https://hal.science/hal-04767217 https://hal.science/hal-04767217v1/document https://hal.science/hal-04767217v1/file/Sci%20Rep%202020.pdf https://doi.org/10.1038/s41598-020-77716-5 |
| Rights: | http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.BE523A0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41598-020-77716-5 |
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