Reference - Detail
| RRC ID | 84191 |
|---|---|
| Author | Breusegem SY, Houghton J, Romero-Bueno R, Fragoso-Luna A, Kentistou KA, Ong KK, Janssen AFJ, Bright NA, Riedel CG, Perry JRB, Askjaer P, Larrieu D. |
| Title | A multiparametric anti-aging CRISPR screen uncovers a role for BAF in protein synthesis regulation. |
| Journal | Nat Commun |
| Abstract |
Progeria syndromes are very rare, incurable premature aging conditions recapitulating most aging features. Here, we report a whole genome, multiparametric CRISPR screen, identifying 43 genes that can rescue multiple cellular phenotypes associated with progeria. We implement the screen in fibroblasts from Néstor-Guillermo Progeria Syndrome male patients, carrying a homozygous A12T mutation in BAF. The hits are enriched for genes involved in protein synthesis, protein and RNA transport and osteoclast formation and are validated in a whole-organism Caenorhabditis elegans model. We further confirm that BAF A12T can disrupt protein synthesis rate and fidelity, which could contribute to premature aging in patients. This work highlights the power of multiparametric genome-wide suppressor screens to identify genes enhancing cellular resilience in premature aging and provide insights into the biology underlying progeria-associated cellular dysfunction. |
| Volume | 16(1) |
| Pages | 1681 |
| Published | 2025-2-16 |
| DOI | 10.1038/s41467-025-56916-5 |
| PII | 10.1038/s41467-025-56916-5 |
| PMID | 39956852 |
| PMC | PMC11830792 |
| MeSH | Aging* / genetics Animals CRISPR-Cas Systems Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Clustered Regularly Interspaced Short Palindromic Repeats DNA-Binding Proteins* / genetics DNA-Binding Proteins* / metabolism Fibroblasts / metabolism Humans Male Mutation Nuclear Proteins* / genetics Nuclear Proteins* / metabolism Progeria* / genetics Progeria* / metabolism Protein Biosynthesis* / genetics |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 41 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm1502 |