We may never know what primordial molecule gave birth to the very first organisms on Earth, yet accumulating evidence indicates that RNA is a strong contender—a single type of molecule that might have been the chief carrier of genetic information and the chief catalyst of replication. And this hypothesis—known by its shorthand name, "RNA World"—appears increasingly plausible because of the work of David Bartel.
In 2001, Bartel created an RNA enzyme, or ribozyme, that could synthesize an RNA molecule that was complementary to a template strand—providing dramatic evidence for the idea that an RNA world is, in fact, feasible. At about the same time, he demonstrated that a single RNA molecule can fold into more than one structure and catalyze multiple reactions—showing that a single molecule could potentially evolve into seemingly unrelated enzymes.
Although Bartel's studies of catalysis have changed the way scientists think about RNA and evolution, he is now focused on an additional target: biological regulatory RNAs. Bartel is interested in how small pieces of regulatory RNA, called microRNAs, "silence" genes during development. His laboratory was among those to first report the existence of a large number of microRNAs in animal cells. Bartel and his colleagues have identified more than 100 microRNAs in the nematode (a small worm), and they showed that the human genome contains hundreds of genes that encode these small regulatory RNAs. They also found microRNAs in plants. MicroRNAs reduce the expression of protein-coding genes by targeting the messenger RNAs of these genes for silencing. While searching for silencing RNAs in fungi, Bartel's lab discovered another type of small regulatory RNA, known as heterochromatic siRNAs (short interfering RNAs), which silence the DNA rather than RNA.
Bartel has also been at the forefront of efforts to determine the biological roles of microRNAs. His lab developed methods to predict the genes that are regulated by plant microRNAs, showing that microRNAs primarily control genes involved in plant stem cell identity or developmental patterning. Experiments in several labs, including Bartels, have confirmed that gene silencing by microRNAs is crucial for proper plant development. In mammals, recent analyses by Bartel and colleagues indicated that microRNAs regulate the expression of more than half of the human genes, including many genes important in human cancers and other diseases. Experiments by Bartel and his collaborators have shown that microRNAs play important roles during brain and blood cell development and have illustrated how the microRNA regulation of a cancer gene helps prevent tumors. Bartel's computational and experimental analyses have supported his proposal that microRNAs have a widespread influence on mammalian gene expression and help to define the various mammalian cell types.