Scientists expand knowledge of cell process involved in many diseases

Aug 16, 2011

As part of a joint research effort with the University of Michigan, scientists from the Florida campus of The Scripps Research Institute have for the first time defined the structure of one of the cell's most basic engines, which is required for cell growth, as it assembles from its components.

The study reveals a series of redundant mechanisms that assure production of these critical structures while avoiding any missteps that could lead to their destruction or to the production of incorrect cellular . These findings throw new light on a process that is integrally involved in a number of disease states, including cancer and .

The study, published on August 11, 2011, in the advance online edition of the prestigious journal Science, reveals the structure of an assembly intermediate of the small ribosomal subunit.

, which are large macromolecular machines required for cell growth in all organisms, catalyze the production of proteins in all . They read the carried by messenger RNA, and then catalyze or translate that code into proteins within cells, assembling them from .

Understanding the process of ribosome assembly—which involves almost 200 essential proteins known as "assembly factors" in addition to the four RNA molecules and 78 ribosomal proteins that are part of the mature ribosome—is a potentially fruitful area of research because of the importance of ribosome assembly for . The link between defects in ribosome assembly and cancer clearly points to this pathway as a new target for anti-cancer drugs.

In the current study, the scientists used cryo-electron microscopy to image the 40S ribosome structure.

"This is the best-defined ribosomal assembly intermediate we have ever had with true structural information on the location of each assembly factor," said Katrin Karbstein, an associate professor at Scripps Florida and one of the senior authors of the study. "It will be helpful in determining what's going on in what is still a relatively unknown process."

While most ribosome assembly takes place in the nucleolus, a protein-nucleic acid structure inside the nucleus, the final maturation process occurs in the cytoplasm, the "general" cellular compartment where translation occurs. In the cytoplasm, these pre-mature ribosomal subunits encounter large pools of mature subunits, messenger RNA, and various translation factors.

This cellular stew presents a unique challenge, especially keeping the translation process from acting on the subunits prematurely, which would result in their rapid degradation or in the production of incorrectly assembled proteins, both processes with potentially lethal outcomes for the cell.

The new study shows that that the bound assembly factors cooperate with one another in a highly redundant and multi-pronged approach to prevent such occurrences, chaperoning the pre-40S subunits to keep them from falling victim to the translational apparatus.

"We had thought the role of assembly factors was to help mature this intermediate form of the ribosome," said Karbstein. "But our new research has shown that these assembly factors also prevent a number of unwanted things from happening. If one of these intermediate forms were to bind prematurely to a , there could be no protein produced, or worse, a wrong protein might be produced and that could lead to early cell death."

It's important to note that this is a single snapshot of the late-stage assembly process, Karbstein added. "We know better how the works but this is by no means a final statement," she said.

Explore further: Research helps identify memory molecules

More information: "Ribosome Assembly Factors Prevent Premature Translation Initiation by 40S Assembly Intermediates," Science. www.sciencemag.org/content/ear… nce.1208245.abstract

Related Stories

Scientist uncovers switch controlling protein production

Dec 22, 2010

A scientist from the Florida campus of The Scripps Research Institute has discovered a molecular switch that controls the synthesis of ribosomes. Ribosomes are the large machineries inside all living cells that produce proteins, ...

Biologists probe the machinery of cellular protein factories

Sep 13, 2006

Proteins of all sizes and shapes do most of the work in living cells, and the DNA sequences in genes spell out the instructions for making those proteins. The crucial job of reading the genetic instructions and synthesizing ...

Recommended for you

Research helps identify memory molecules

10 hours ago

A newly discovered method of identifying the creation of proteins in the body could lead to new insights into how learning and memories are impaired in Alzheimer's disease.

Computer simulations visualize ion flux

11 hours ago

Ion channels are involved in many physiological and pathophysiological processes throughout the human body. A young team of researchers led by pharmacologist Anna Stary-Weinzinger from the Department of Pharmacology ...

Neutron diffraction sheds light on photosynthesis

11 hours ago

Scientists from ILL and CEA-Grenoble have improved our understanding of the way plants evolved to take advantage of sunlight. Using cold neutron diffraction, they analysed the structure of thylakoid lipids found in plant ...

DNA may have had humble beginnings as nutrient carrier

Sep 01, 2014

New research intriguingly suggests that DNA, the genetic information carrier for humans and other complex life, might have had a rather humbler origin. In some microbes, a study shows, DNA pulls double duty ...

Central biobank for drug research

Sep 01, 2014

For the development of new drugs it is crucial to work with stem cells, as these allow scientists to study the effects of new active pharmaceutical ingredients. But it has always been difficult to derive ...

User comments : 0