We may never know what primordial molecule gave birth to the types of organisms that currently inhabit the Earth, yet accumulating evidence indicates that RNA is a strong contender—a single type of molecule that would have been both the…
We may never know what primordial molecule gave birth to the types of organisms that currently inhabit the Earth, yet accumulating evidence indicates that RNA is a strong contender—a single type of molecule that would have been both the carrier of genetic information and the catalyst that replicated this information. This hypothesis—known by its shorthand name, "RNA World"—has become increasingly favored because of the early 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 the types of catalysis that potentially occurred on the early earth have changed the way scientists think about RNA and evolution, he is best known for his more recent studies of the roles that regulatory RNAs play in contemporary biology. Bartel has been especially interested in small snippets of RNA, called microRNAs, which direct the "silencing" of messenger RNAs of genes in plants and animals. Bartel's laboratory co-discovered the abundance of microRNAs in animal cells and has since been interested in their genomics and evolution. For instance, Bartel and his colleagues identified many of the microRNA genes of experimental animals, such as nematodes (small worms), fruit flies, and mice, and showed that the human genome contains hundreds of genes that encode these small regulatory RNAs. They also found microRNAs in very distantly related animals, including sponge, implying that these small regulatory RNAs have been shaping gene expression since the dawn of multicellular animal life. Similarly, they discovered miRNAs in plants and identified most of the known microRNAs of Arabidopsis (a small flowering plant used for molecular genetic analyses) as well as very distantly related land plants. While searching for microRNAs, Bartel's lab also discovered other types of silencing RNAs in animals, plants, and fungi. For example, in fungi, they found small regulatory RNAs, known as heterochromatic siRNAs (short interfering RNAs), which help silence DNA rather than RNA. Biologists had originally thought that when silencing gene expression in mammalian cells, microRNAs were reducing the amount of protein translated from messenger RNAs without substantially changing messenger RNA levels. Bartel's experiments, which simultaneously examined the effects of microRNAs on hundreds of targeted messenger RNAs, have overturned this idea, showing that most of the silencing is explained by reducing the levels of the messenger RNAs rather than reducing their translation. Bartel has also been at the forefront of efforts to determine the biological functions of microRNAs. His lab initially identified the genes that are regulated by plant microRNAs, showing that plant microRNAs primarily control genes involved in plant stem cell identity or developmental patterning. Experiments in several labs, including Bartel's, have confirmed that gene silencing by microRNAs is crucial for proper plant development. Insights by Bartel and colleagues into how microRNAs recognize messenger RNAs of animal cells have revealed a surprisingly widespread influence of microRNAs on mammalian gene expression. For example, their identification and analysis of the types of interactions that have been retained throughout much of mammalian evolution have indicated that microRNAs regulate the output of most human genes, including many important in cancers and other diseases. Additional experiments by Bartel and his collaborators have shown that microRNAs play critical roles during brain and blood-cell development and have illustrated how the microRNA-mediated repression of a cancer gene helps prevent tumors.