Proteins usually have to do the grunt work in cells, such as degrading used-up molecules and flipping switches for protein production. Now, researchers have discovered an RNA molecule that not only codes for an enzyme, but shuts itself off when the enzyme has done enough work. This finding fuels the argument that many enzymatic activities found in proteins originated in RNA.
Cells make proteins by copying DNA into a messenger RNA (mRNA) blueprint, which a cellular apparatus uses to construct the protein. These factories, called ribosomes, need a way to turn off production when enough of a particular product has been made. Fabrication often stops when the finished protein sticks to a particular spot on its mRNA template, impeding the ribosome from using the mRNA. But not everything cells need has an mRNA blueprint. For example, bacteria synthesize the small, non-protein molecule thiamin (vitamin B1) from scratch using several enzymes, and researchers have puzzled over what turns the mRNA for those enzymes off once they've reached their quota--the enzymes don't bind to mRNA and researchers' search had come up empty for a protein intermediary that might bind thiamin and then turn off the mRNA.
Biochemist Ronald Breaker at Yale University suspected thiamin itself might do the deed--a hypothesis that runs contrary to the longstanding notion that only proteins can bind mRNA and turn off protein production. Breaker's team fashioned mRNAs to test their idea. The first half of the mRNAs contained sequences for two of the thiamin-producing enzymes. The second half carried the plans for another protein the researchers could readily measure. The team found that the mRNAs embraced the thiamin and its active form, thiamin-PP. Moreover, when the researchers mixed the half-and-half mRNAs with ribosomes in a test tube, they found that thiamin suppressed protein synthesis at least 18-fold. Additional experiments revealed that when thiamin bound to the mRNA, the mRNA changed its shape to hide key sequences needed for the protein-making machinery, they report 17 October in Nature. Breaker's team also found a similar shape change controls the synthesis of vitamin B12, which they reported last September in Chemistry and Biology.
Breaker says finding similar "mRNA switches" in more advanced organisms would support the idea that they were left over from a preprotein world dominated by RNA. Molecular biologist Jack Szostak of Harvard University Medical School in Boston says that even though researchers have known about RNA enzymes for 20 years, people still don't consider RNA as versatile as proteins. In the lab, RNA has superpowers to take on any shape, he explains, but it hasn't been clear whether that capacity is used in nature. "Now we find it is," says Szostak. "It's very satisfying."