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Process leading to protein diversity in cells important for proper neuron firing
Date:11/18/2010

PHILADELPHIA Cells have their own version of the cut-and-paste editing function called splicing. Researchers at the University of Pennsylvania School of Medicine have documented a novel form of splicing in the cytoplasm of a nerve cell, which dictates a special form of a potassium channel protein in the outer membrane. The channel protein is found in the dendrites of hippocampus cells -- the seat of memory, learning, and spatial navigation -- and is involved in coordinating the electrical firing of nerve cells. Dendrites, which branch from the cell body of the neuron, play a key role in the communication between cells of the nervous system.

The diversity of proteins within the human body -- in this case neurons arises from the many ways that messenger RNAs (mRNA) can be spliced and reconnected. To start, a gene is copied into mRNA, which contains both exons (protein-coding regions) and introns (non-coding regions). Special molecules cut out introns and merge together the remaining exon pieces, resulting in an mRNA capable of being translated into a specific protein.

The study, published this week online in the Proceedings of the National Academy of Sciences, is the first to show that introns that are retained in mRNA can direct the choice of protein sequences to be included in the final protein prior to translation into a full protein. Normally introns would be spliced out in the nucleus. Diseases such as epilepsy that are based on electrical misfiring in the brain could be targets of manipulation of such cytoplasmic splicing.

In a series of previously published research, the lab of senior author James Eberwine, PhD, established that splicing of RNA occurs outside of the nucleus in different parts of a nerve cell, specifically in the cytoplasm and dendrites. Eberwine is the Elmer Holmes Bobst professor of Pharmacology and co-director of the Penn Genome Frontiers Institute.

The group went on to discover that re
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

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