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RSRF-funded research yields novel function for Rett syndrome gene

Huda Zoghbi, of Baylor College of Medicine and the Howard Hughes Medical Institute and Juan Young, also of Baylor and colleagues report in the online Early Edition of the Proceedings of the National Academy of Science, posted the week of October 17, 2005, that the Rett Syndrome gene, MECP2, regulates RNA splicing. This work was funded in part by the Rett Syndrome Research Foundation (RSRF).

Rett Syndrome (RTT) is a severe neurological disorder diagnosed almost exclusively in girls. Children with RTT appear to develop normally until 6 to 18 months of age, when they enter a period of regression, losing speech and motor skills. Most develop repetitive hand movements, irregular breathing patterns, seizures and extreme motor control problems. RTT leaves its victims profoundly disabled, requiring maximum assistance with every aspect of daily living. There is no cure.

RTT is caused by mutations in a gene (MECP2) that regulates expression of other genes. Genes are made up of long stretches of nucleotide bases that are divided into exons (sequences that code for protein) and introns (non-coding sequences). Genes make proteins in a multi-step process. The first, called transcription, takes place in the cell nucleus where DNA is copied into RNA. The second step involves cutting out the introns and pasting together the exons to make up the mature RNA. This RNA is then translated into proteins.

There is a wealth of data to suggest that MECP2 is a transcriptional repressor, meaning it turns off or down-regulates the production of other proteins by shutting down transcription. To date, a handful of MECP2 target genes have been identified.

The paradigm of one gene to one protein has recently given way to the realization that genes encode multiple proteins through a process called alternative splicing, whereby different combinations of exons are pasted together. Furthermore, genes can also have multiple functions. This phenomenon helps to explain
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Contact: Monica Coenraads
monica@rsrf.org
203 445 9233
Rett Syndrome Research Foundation
18-Oct-2005


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