Study by Israeli scientists provides insight o...( oscope. Their task was made dif...)

Their task was made difficult by the fact that spliceosomes in living cells are made up of four identical modules strung together like beads on a strand of RNA, each a miniature spliceosome capable of splicing on its own. The connections between the modules tend to be flexible, allowing the position of the units to vary in relation to each other. Thus pinning down a definitive shape and structure for the whole complex has been, until now, nearly impossible.

The team found a way to cut the RNA connections between the modules without harming the integral short strands of RNA that are essential to the splicing process, so they could study them individually. Split-second freezing at very low temperatures allowed the scientists to view the spliceosome units in as close to a natural state as possible. From thousands of images, each at a slightly different angle, a composite 3-D structure of the spliceosome was built up.

The revealed structure has two distinct, unequal halves surrounding a tunnel. The larger part appears to contain proteins and the short segments of RNA, while the smaller half is made up of proteins alone. On one side, the tunnel opens up into a cavity, which the researchers think functions as a holding space for the fragile RNA waiting to be processed in the tunnel itself.

What they didn't see may be as important as what they saw. Whereas researchers examining splicing in test tubes saw evidence of a complicated sequence of events in which the spliceosome machinery assembles itself anew for each splicing job, the team's investigations of spliceosomes from live cells found splicing to take place in pre-formed machines. This fits in with what is known about the way cells optimize their workload. "It's much more efficient to have a machine on hand, ready to go, than to build a new one each time," they noted.

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Contact: Jerry Barach
jerryb@savion.huji.ac.il
972-2-5882904
The Hebrew University of Jerusalem
9-Sep-2004