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Mutant biological machine makes proteins but can't let go

Writing in the May 28 issue of Cell, Johns Hopkins researchers report that four critical components of cells' protein-building machine don't do what scientists had long assumed.

The machine, called the ribosome, is a ball of RNA (DNA's cousin) surrounded by proteins. In the RNA center, genetic instructions are read, the right protein building block is added onto a growing chain, and at the appropriate time the chain is snipped and released.

But while researchers have long known that the ribosome builds proteins, little is understood about exactly how it adds to growing proteins and how it releases the finished product.

In the hunt for these details, scientists have focused on four RNA building blocks, or nucleotides, deep within the machine that are identical in every species, from bacteria to humans. Because they sit where the protein chain is actually built, these "universally conserved" nucleotides in the ribosome were thought to help that process.

Unexpectedly, Johns Hopkins researchers have discovered that these four nucleotides are not important for building the protein, but instead help release the finished product. In laboratory experiments, the researchers found that ribosomes with these key spots changed could put proteins together as well as normal ribosomes, but let go of the finished product much more slowly.

"Most scientists have said that these four nucleotides must be critical for synthesis of the growing protein because of their location, and we fully expected that our studies would prove that to be true," says Rachel Green, Ph.D., associate professor of molecular biology and genetics and a Howard Hughes Medical Institute associate investigator. "We were shocked that they appear to play very little if any role in building proteins, and instead normally speed the protein's release at the right time.

"Our finding underscores the idea that if you build a well-defined system to study a biologic question,
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
27-May-2004


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