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A splice of life
Date:3/27/2009

Waltham, MAIn a new study this week in Nature, researchers at Brandeis University and the MRC Laboratory of Molecular Biology (Cambridge, U.K.) for the first time shed light on a crucial step in the complex process by which human genetic information is transmitted to action in the human cell and frequently at which point genetic disease develops in humans.

The scientists report that they were able to crystallize a very large complex of a macromolecular "machine" in the human cell and determine its structure or what it actually looks like, thereby zeroing in on the process of genetic encoding. Importantly, 15 to 20 percent of all human genetic disorders, including muscular dystrophy, are caused by defects in this genetic encoding process known as RNA splicing.

Using x-ray crystallography, the scientists for the first time were able to create a three-dimensional structure of an integral complex of the human spliceosome, which consists of specialized RNA and protein subunits. The spliceosome's job is to modify the message relayed from our genetic materialDNAby clipping, or splicing, genetic bits in such a manner that they are acceptable for translation into protein. Importantly, the spliceosome also rearranges the genetic bits of the message in such a way that it can generate multiple and varied proteins which can and do have dramatic effects on human development, said lead author and Brandeis biochemist Daniel Pomeranz Krummel.

"The process of RNA splicing is vital to human cell development and survival," said Pomeranz Krummel. "In this process, the regions of our DNA encoding for protein are removed from non-encoding regions and brought togetherquite often in alternative arrangements. Defects in this process can have disasterous repercussions in the form of genetic disorders," said Pomeranz Krummel, adding that neuronal development can be particularly affected when things go awry. Indeed, defects in this process have recently
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Contact: Laura Gardner
gardner@brandeis.edu
781-736-4204
Brandeis University
Source:Eurekalert

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