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Israeli scientists reveal the plan of a key cellular machine

A team of scientists from the Weizmann Institute of Science and the Hebrew University of Jerusalem has revealed the structure of a cellular editor that "cuts and pastes" the first draft of RNA straight after it is formed from its DNA template. Many diseases appear to be tied to mistakes in this process, and understanding the workings of the machinery involved may lead to the ability to correct or prevent them in the future.

Since the discovery, around 25 years ago, that the bits of DNA in the genes that code for protein formation are interspersed with "filler" segments that have no known function, scientists have worked to understand the process by which the right sequences are lifted out and strung together to make a coherent set of instructions. This act, referred to as "RNA splicing," takes place in the "spliceosome" situated in the cell nucleus. A large complex of proteins and short strands of RNA, the spliceosome distinguishes the beginnings and ends of coded segments, precisely cutting and stitching them together. Alternative splicing, which underlies the huge diversity of proteins in the body by allowing segments of the genetic code to be strung together in different ways, takes place in the spliceosome as well.

The team consisted of husband-and-wife scientists Prof. Ruth Sperling of the Genetics department of the Hebrew University and Prof. Joseph Sperling of the Organic Chemistry Department of the Weizmann Institute, Ruth's graduate student Maia Azubel, and Sharon Wolf of the Chemical Research Support Department at the Institute. They produced the most detailed 3-D representation of the spliceosome's structure to date with their study, published today in Molecular Cell.

Rather than follow previous attempts to unravel the workings of the splicing mechanism by studying spliceosomes created in test tubes, they managed to take spliceosomes directly from living cells and examine them under an electron microscope.

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Contact: Alex Smith
asmith@jgordanassociates.com
212-367-3892
American Committee for the Weizmann Institute of Science
9-Sep-2004


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