PXD067852 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | CRISPR activation of the ribosome-associated quality control factor ASCC3 ameliorates fragile X syndrome phenotypes in mice |
| Description | Loss of fragile X messenger ribonucleoprotein (FMRP) causes fragile X syndrome (FXS), an inherited neurodevelopmental disorder resulting in intellectual disability and autism-spectrum disorder. Despite the prevalence of the FXS, the molecular function of FMRP remains uncertain. Here, we showed that FMRP regulates collided ribosomes. Activating signal cointegrator 1 complex subunit 3 (ASCC3), an early-acting ribosome-associated quality control (RQC) factor, was identified as an FMRP-interacting protein. Mechanistically, FMRP recruits ASCC3 to collided ribosomes and either positively or negatively regulates translation, depending on transcript context. Disease-associated ASCC3 variants that perturbed ASCC3-FMRP interaction were defective in ribosome association and handling of collided ribosomes. In FXS patient cells and mouse models of FXS, ASCC3 abundance was reduced, and Clustered Regularly Interspaced Short Palindromic Repeats-mediated activation (CRISPRa) of ASCC3 overcame challenges to conventional gene delivery approaches presented by the sheer size of ASCC3 and rescued synaptic defects and behavioral deficits. In conclusion, these data implicated FMRP in the handling of collided ribosomes to maintain protein homeostasis during neurodevelopment and synaptogenesis and showed. Proof-of-concept that targeting RQC may offer alternative treatment strategies for FXS. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-04-20 |
| AnnouncementXML | Submission_2026-04-19_16:23:16.696.xml |
| DigitalObjectIdentifier | https://doi.org/10.6019/PXD067852 |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | JI Geng |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | LTQ Orbitrap |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2025-08-28 12:40:37 | ID requested | |
| ⏵ 1 | 2026-04-19 16:23:17 | announced | |
Publication List
| 10.6019/PXD067852; |
| Geng J, Wang X, Pan J, Khan D, Pimcharoen S, Zhang Y, Mosammaparast N, Hirose S, Petrucelli L, Brandman O, Qi LS, Lu B, CRISPR activation of the ribosome-associated quality control factor ASCC3 ameliorates fragile X syndrome phenotypes in mice. Sci Transl Med, 17(819):eadq3551(2025) [pubmed] |
| 10.1126/scitranslmed.adq3551; |
Keyword List
| submitter keyword: HEK293T |
Contact List
| Bingwei Lu |
|---|
| contact affiliation | Pathology, Stanford University |
| contact email | bingwei@stanford.edu |
| lab head | |
| JI Geng |
|---|
| contact affiliation | Stanford Univeristy |
| contact email | jigeng@stanford.edu |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD067852
- Label: PRIDE project
- Name: CRISPR activation of the ribosome-associated quality control factor ASCC3 ameliorates fragile X syndrome phenotypes in mice
