Cellular editor

Knowing its genetic structure will help cure diseases

 
Last Updated: Saturday 04 July 2015

scientists from Israel-based Hebrew University and the Weizmann Institute of Science have found the genetic structure of a 'cellular editor' that cuts and pastes the first draft of rna (ribonucleic acid) straight after it is formed from its dna template. Many diseases are linked to mistakes in this process; therefore a understanding of the process may help develop the ability to treat or prevent the diseases.

About 25 years ago, it was discovered that bits of dna (in genes that code for protein formation) are interspersed with filler segments that have no known function. Since then scientists have tried 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. The spliceosome distinguishes the beginnings and ends of coded segments, precisely cutting and stitching them together very neatly.

The Israeli scientists, Ruth Sperling and Joseph Sperling, produced a detailed 3-d representation of the spliceosome's structure during their study, which is published in the journal Molecular Cell. Rather than following the 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.

But 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, with each being 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. 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.

As per the scientists, the 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.

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 optimise their workload. It is much more efficient to have a machine on hand, ready to go, than to build a new one each time, the scientists noted.

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