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Mispairs in genetic material make protein synthesis more efficient

MADISON- The wealth of information contained in a strand of genetic material boils down to sequences of matched pairs of nucleotides that cellular machinery decodes to construct proteins.

Writing today in The Proceedings of the National Academy of Sciences, a University of Wisconsin-Madison bacteriologist reveals that mispaired nucleotides in transfer RNA actually make the molecule more adroit, enhancing its ability to build proteins. The paper also illustrates the dynamic nature of genetic material, which is not flat, like an illustration in a textbook, but twists and bends as it interacts with cellular machinery.

The mispairs, also called "wobble pairs," do not bind together as tightly as matched pairs bind, making transfer RNA "a compressed spring ready to be sprung," according to William McClain, a professor of bacteriology in the UW-Madison's College of Agricultural and Life Sciences and the author of the PNAS paper. He notes that specific transfer RNA mispairs, which likely originally arose through natural mutation, are highly conserved across all kingdoms of life, providing evidence that they play an important role in making the molecule more reactive.

Genetic information is encoded in DNA, which is made up of matched base pairs of adenine and thymine, and guanine and cytosine - commonly denoted with the letters A, T, G and C. Cellular machinery transcribes the information from DNA into RNA - where the base uracil replaces thymine -- and then translates the coded data into proteins, which form the building blocks of life.

Scientists have long known that transfer RNA - which adds amino acids to a growing chain during protein synthesis - holds a surprising secret when it comes to its base pairs: occasionally, instead of the expected A-U or G-C pairs, there exists instead a mispair of A-C or G-U. However, the role and importance of mispairs has never been well understood, says McClain.

McClain, who has spent his caree
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Contact: William McClain
wmcclain@wisc.edu
608-262-3054
University of Wisconsin-Madison
6-Mar-2006


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