Ability To Smell Food Regulated By Enzyme's Interaction With RNA Interference Pathway

Brenda L. Bass, Ph.D., professor of biochemistry at the U School of Medicine and a Howard Hughes Medical Institute investigator, and Leath A. Tonkin, a graduate student in her lab, published their findings in the Dec. 5 issue of the journal Science.

With the help of a tiny worm, C. elegans, Bass and Tonkin discovered that ADAR, an enzyme abundant in the nervous system, interacts with a pathway called RNAi (RNA interference). When it's functioning properly, RNAi, which was discovered in 1998, ensures that certain genes are turned on in some cells and turned off in others.

C. elegans that have mutations in their ADAR genes have behavioral defects, according to Bass. For example, mutant worms that lack ADARs have trouble finding food. When placed near food a normal worm crawls quickly to the food but an ADAR mutant may crawl in a completely different direction. To see if ADAR functions were related to the RNAi pathway, Bass and Tonkin made strains of the worm with mutations in both the ADAR genes and in genes required for RNAi.

"Remarkably, in these worms, the behavioral defects associated with the mutations in the ADAR genes were eliminated," Bass said. "This suggests that ADARs intersect with the RNAi pathway and that many of the behavioral defects of ADAR mutants are caused by aberrant RNAi."

RNA is a nucleic acid that is an essential component of all cells. In a process called transcription, the information in our DNA genes is passed to RNA. A second process called translation allows the information in RNA to be turned into protein. Typically, one gene has the information for one protein, but with the help of "editing" enzymes such as ADAR, multiple proteins can be made from one gene.

ADARs enable RNA to produce different proteins by altering the sequence of nucleotides that contain the information for making a protein. That had been considered ADARs' most important function, but the research of Bass and Tonkin shows that ADARs perform other jobs as well.