A team of scientists from the Weizmann Institute of Science in Rehovot and from the Hebrew University of Jerusalem has gained insight into how the DNA code is turned into instructions for protein construction.
The researchers 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.
For the past 25 years, scientists have worked to understand the process by which the right sequences are lifted out of the DNA and strung together to make a coherent set of instructions for protein construction. 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.
The team behind the discovery produced the most detailed 3-D representation of the spliceosome's structure to date with their study, published this week 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. Split-second freezing at very low temperatures allowed the scientists to view the spliceosome units in as close to a natural state as possible.
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.
The researchers involved included 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.
The researchers 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.
For the past 25 years, scientists have worked to understand the process by which the right sequences are lifted out of the DNA and strung together to make a coherent set of instructions for protein construction. 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.
The team behind the discovery produced the most detailed 3-D representation of the spliceosome's structure to date with their study, published this week 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. Split-second freezing at very low temperatures allowed the scientists to view the spliceosome units in as close to a natural state as possible.
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.
The researchers involved included 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.