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April 27, 1998

Ribosome study yields new clues to protein synthesis

By Tim Stephens

Researchers in the lab of Harry Noller, Sinsheimer Professor of Molecular Biology, have taken another key step toward solving the puzzle of how ribosomes carry out protein synthesis, a fundamental process in all living cells. The new study, published in the April 10 issue of the journal Science, identified a key stretch of RNA at the site of protein synthesis on the ribosome.

Ribosomes are intricate molecular machines that play a central role in translating the genetic code contained in DNA into proteins of all kinds. Proteins--as structural elements, chemical messengers, and enzymes--are essential players in the life of the cell. The ribosome itself is made up of both protein and RNA molecules.

Noller's group has been steadily advancing the theory that the ribosome's RNA component plays an active role in the enzymatic reaction that joins one protein building block to another. Enzymes--the catalysts of biochemical reactions--are almost always proteins. So it would be extraordinary if an enzyme that plays a central role in biology turned out to be composed of RNA.

Rachel Green, whose work as a postdoctoral researcher in Noller's lab led to the new findings, said the study adds more weight to the accumulating evidence in favor of an active role for ribosomal RNA in the reactions that build proteins.

"People have been studying active ribosomes for 30 years, but we still don't know what the catalytic element is," said Green, now an assistant professor of molecular biology and genetics at Johns Hopkins University School of Medicine in Baltimore.

Researchers have given this unknown catalytic element a name--peptidyl transferase--and are attempting to locate it within the three-dimensional structure of the ribosome. Green's study brings to three the number of pieces of RNA that have been unambiguously localized to the active site of peptidyl transferase. No proteins have so far been shown to be directly involved, but neither have they been ruled out as active components, Green said.

"This is another nail in the coffin, but it doesn't prove there are no proteins," Green said.

Green hopes to develop new techniques for studying ribosomes based on her findings, which suggest a way to label ribosomes and distinguish active from inactive forms in the test tube. Green said she wants to create catalytic RNA in the absence of proteins using genetic selection techniques.

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