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Wobble hypothesis stands up, NC state researcher finds

A recent finding by a North Carolina State University biochemist advances the fundamental biology of how genetic information, encoded in DNA, is decoded for the production of proteins.

Dr. Paul F. Agris, professor of biochemistry at NC State, and academic colleagues from England and Poland show concrete evidence in favor of the 1966 "Wobble Hypothesis" offered by Francis Crick, the co-founder of the DNA molecule and its double-helix structure, and Agris' own "Modified Wobble Hypothesis" posed in 1991.

The scientists used x-ray crystallography of the cell's protein-manufacturing unit, the ribosome, to provide a visual snapshot of the decoding process.

The research is published in the December 2004 edition of Nature Structural and Molecular Biology.

The Wobble Hypothesis was Crick's attempt to make sense of how the cell decodes the genetic information of DNA the molecule that constitutes all the genetic information in a cell and then, from that information, makes biologically active proteins, Agris said.

DNA has 61 three-letter codes that are translated by transfer RNA (tRNA) into amino acids; proteins are made of amino acids. But there are only 20 natural amino acids. Squaring the disparity between the number of codes and the number of amino acids there are three times as many codes as there are amino acids became a hurdle for Crick and other early geneticists, Agris explained.

Crick attempted to clear this hurdle with the Wobble Hypothesis. He based this theory on the first report of a tRNA molecule's chemical structure discovered by Robert Holley in 1963.

Normally, RNA molecules are composed of four nucleosides: adenosine, guanosine, cytosine and uridine (A,G,C,U). But the tRNA molecule Holley studied included a modified nucleoside called inosine (I), Agris says. Seeing this inosine in an important area of the tRNA molecule an area that read the three-letter DNA codes when the cell synthesizes proteins
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3-Dec-2004


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