Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How DNA code is turned into instructions for protein construction

10.09.2004


A team of scientists from the Hebrew University of Jerusalem and the Weizmann Institute of Science 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 Weizmann Institute. They produced the most detailed 3-D representation of the spliceosome’s structure to date with their study, published in the current edition of the journal 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.



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.

Jerry Barach | alfa
Further information:
http://www.huji.ac.il

More articles from Life Sciences:

nachricht During HIV infection, antibody can block B cells from fighting pathogens
14.08.2018 | NIH/National Institute of Allergy and Infectious Diseases

nachricht First study on physical properties of giant cancer cells may inform new treatments
14.08.2018 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

Im Focus: World record: Fastest 3-D tomographic images at BESSY II

The quality of materials often depends on the manufacturing process. In casting and welding, for example, the rate at which melts solidify and the resulting microstructure of the alloy is important. With metallic foams as well, it depends on exactly how the foaming process takes place. To understand these processes fully requires fast sensing capability. The fastest 3D tomographic images to date have now been achieved at the BESSY II X-ray source operated by the Helmholtz-Zentrum Berlin.

Dr. Francisco Garcia-Moreno and his team have designed a turntable that rotates ultra-stably about its axis at a constant rotational speed. This really depends...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

'Building up' stretchable electronics to be as multipurpose as your smartphone

14.08.2018 | Information Technology

During HIV infection, antibody can block B cells from fighting pathogens

14.08.2018 | Life Sciences

First study on physical properties of giant cancer cells may inform new treatments

14.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>