Genetic removal of p70 S6K1 corrects coding sequence length-dependent alterations in mRNA translation in fragile X syndrome mice
Abstract
Fragile X syndrome (FXS) is the most prevalent inherited form of intellectual disability. FXS is caused by loss of fragile X mental retardation protein (FMRP), an RNA-binding protein that represses translation. Correspondingly, genetic removal of the translation-stimulating p70 S6 kinase 1 (S6K1) in FXS mice restores translational homeostasis and rescues synaptic and behavioral phenotypes. However, the mechanisms of FMRP function are in dispute, and the molecular basis of the rescue in protein synthesis with reduction of S6K1 is unknown. Here, by carrying out ribosome profiling and molecular assays, we reveal the molecular mechanisms by which reduction of S6K1 corrects altered protein synthesis in FXS. Our study elucidates the molecular foundations of a model for correction of pathophysiological features of FXS.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 27, 2021
- Source ID
- 10.1073/pnas.2001681118
Entities
People
- Eric Klann
- Francesco Longo
- Sameer Aryal
Organizations
- National Institutes of Health
- New York University
- United States Department of Defense