Structures of two aptamers with differing ligand specificity reveal ruggedness in the functional landscape of RNA

摘要

DNA’s iconic double helix has made it possibly the most widely recognized biological molecule. The closely related RNA, however, is less well known but just as vital. In contrast with DNA’s typical rigid structure, RNA is more flexible and can fold into a wide range of shapes; this allows RNA molecules to have many jobs. Some RNA molecules form structures called riboswitches. As the name suggests, these act as molecular switches that help cells to respond to the presence of important small molecules. When a riboswitch encounters the right molecule, it changes shape, which in turn changes how the cell behaves. It is very difficult, if not impossible, to predict how a riboswitch recognizes its preferred small molecule. To address this, scientists use a technique called X-ray crystallography to directly examine the riboswitch’s structure. Knappenberger, Reiss and Strobel have now determined the structures of two recently discovered riboswitches. The two switches detect molecules called PRPP and ppGpp, respectively. These riboswitches are structurally similar to one that binds to a very different type of chemical called guanidine. The aim was to understand how similar switches respond to different signals. The results reveal that a PRPP riboswitch could become a ppGpp riboswitch just by making a single change to the RNA sequence. Many scientists believe RNA preceded DNA and proteins in some of the earliest organisms on Earth. Understanding how RNAs have evolved and diversified could thus help to understand how early life developed. The results may also help to design synthetic riboswitches for a variety of uses. Since many riboswitches are unique to bacteria, this work could also contribute to the search for new antibiotics.