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Spying on a cellular director in the cutting room
Date:3/21/2010

ANN ARBOR, Mich.---Like a film director cutting out extraneous footage to create a blockbuster, the cellular machine called the spliceosome snips out unwanted stretches of genetic material and joins the remaining pieces to fashion a template for protein production.

But more than box office revenues are at stake: if the spliceosome makes a careless cut, disease likely results.

Using a new approach to studying the spliceosome, a team led by University of Michigan chemistry and biophysics professor Nils Walter, collaborating closely with a team led by internationally recognized splicing experts John Abelson and Christine Guthrie of the University of California, San Francisco, spied on the splicing process in single molecules.

The research is scheduled to be published online March 21 in Nature Structural and Molecular Biology.

Since its Nobel Prize-winning discovery in 1977, gene splicing has been studied in a number of organisms, including yeast and human cells, using both genetic and biochemical approaches. While these methods can yield snapshots, they can't monitor the ongoing process. The new study, which utilizes a technique called fluorescence resonance energy transfer (FRET) and a sophisticated microscope that watches single molecules in action, allows researchers to observe in real time the contortions involved in spliceosome assembly and operation.

By molecular-scale standards, the spliceosome is a monster of a machine, made up of five RNA and 100 or more protein subunits that agilely assemble, step-by-step, into the giant complex when it's time to carry out its work.

True to the movie director analogy, the spliceosome not only wields the scissors, it's also "the brain that decides where to cut," Walter said. The "footage" it works on is the genetic material contained in RNA molecules.RNA carries coded instructions for producing the proteins our body needs for building and repairing tissues,
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Contact: Nancy Ross-Flanigan
rossflan@umich.edu
734-647-1853
University of Michigan
Source:Eurekalert

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