Fragile X Chromosome made visible by Atomic Force MicroscopyDR. BEN OOSTRA/VISUAL UNLIMITED, INC.
J.C. Darnell et al., “FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism,”Cell, 146:247-61, 2011. Free F1000 Evaluation
Fragile X syndrome, which is associated with autistic behavior, is almost always caused by loss of the protein FMRP. Although researchers knew that FMRP binds polyribosomes and mRNA to regulate synaptic plasticity, the mechanism was unknown. Robert Darnell at Rockefeller University and colleagues showed that FMRP regulates protein synthesis by reversibly stalling translation in neurons.
Darnell’s team started by identifying the mRNAs that FMRP binds. They zapped cells with UV to covalently bind FMRP and any mRNAs in direct contact and sequenced more than 800 of the bound mRNA transcripts. They noticed that FMRP-bound RNAs were also bound to ribosome complexes, which usually indicates ...