Genetic switch potential key to new class of antibiotics

Researchers have determined the structure of a key genetic mechanism at work in bacteria, including some that are deadly to humans, in an important step toward the design of a new class of antibiotics, according to an accelerated publication that appeared online today as a "paper of the week" in the Journal of Biological Chemistry.

Information stored in genes is translated or expressed into proteins, the workhorse molecules that make up the body’s structures and carry its messages. In the classical view of gene expression, instructions stored in deoxyribonucleic acid (DNA) chains are copied into messenger ribonucleic acids (mRNAs). The mRNAs are then transported to ribosomes that pair them with transfer RNAs that contribute amino acids into a protein chain, thereby decoding the gene. In recent years, groundbreaking work has revealed that RNA is much more than a passive middleman, and instead exerts decisive control over expression.

Researchers in the Breaker lab at Yale and Nudler lab at NYU reported in 2002 that regulatory mechanisms arising from riboswitches regulate gene expression at the level of the mRNA by changing shape in ways that govern the genetic decoding process. Clarifying the principles of how riboswitches change their spatial organization, which entails binding to a small signaling partner, promises to inform the design of a new class of antibiotics. The current study clarified for the first time the exact structure of nature’s smallest known riboswitch, and detailed how its structures control life processes in bacteria.

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