A paper published online in Nature Neuroscience explores the mechanisms underlying fragile X syndrome -- the most common inherited form of mental retardation.
This disorder is caused by loss of a protein, dubbed FMRP, which interacts with messenger RNAs. (mRNAs are the templates that a cell "reads" to correctly build specific proteins.) The details of how FMRP affects mRNAs and protein synthesis, and how subtle misregulation in absence of FMRP causes mental retardation, are still unclear.
Claudia Bagni and Kirsten S Dickson and colleagues now report that FMRP stabilizes the mRNA that encodes the protein PSD-95. PSD-95 is crucial for the structure and function of neural synapses. In the brains of mice lacking FMRP, the authors found that the PSD-95 mRNA was rapidly degraded. The level of PSD-95 protein was reduced especially in the hippocampus, a structure crucial for learning, memory and certain kinds of reasoning.
This work suggests an important role for mRNA stabilization in the circuit wiring and communication of nerve cell networks. Though it is unlikely that all fragile X mental retardation symptoms can be explained by instability of PSD-95 mRNA, it may well represent an important part of the disease mechanism.
Claudia Bagni (Universita di Roma, Italy)
Kirsten S. Dickson (University of Edinburgh, UK)
Abstract available online.
(C) Nature Neuroscience press release.
Message posted by: Trevor M. D'Souza
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