A chemical glimpse into life’s origins

Image shows the active centre of the new ribozyme, where the chemical reaction takes place. This reveals the mechanism by which the ribozyme accelerates the formation of the new carbon-nitrogen bond.

One widely accepted theory is that proteins were too complicated to make in the early stages, and that a molecule called RNA (very similar to its more-famous cousin DNA) was the key player that directed the metabolism of primitive cells. In this “RNA world”, RNA would both encode genetic information (much like DNA does now), but also speed up cellular chemical reactions (as now done by proteins, called enzymes). RNA is chemically rather more simple than proteins, so it’s a challenge to conceive how it could act in this way. Yet RNA enzymes (called ribozymes) do exist in modern biology, including the molecular machine that makes proteins in the cell.  But in general, contemporary ribozymes carry out a rather limited range of chemistry, and the RNA world would have required ribozymes with a much wider repertoire. For example, ribozymes would have been needed that mediate “difficult” chemical reactions, like joining a carbon atom to another carbon, or to a nitrogen atom. These would have been essential to build up the complex molecules required for life. 

While there is no time machine to allow us to get samples from the RNA world, we can ask if we can find ribozymes by what we might call “test tube evolution” that might tell us that in principle RNA can do such reactions. One such RNA has been found that can make a new carbon-nitrogen bond. In a UK-Chinese collaboration the groups of Professor David Lilley in Dundee, and Dr Lin Huang in Sun Yat-sen University in Guangzhou have solved the atomic structure of this ribozyme. This is like sneaking a look under the hood of the ribozyme to see how it performs its chemistry. In fact the structure immediately suggests a mechanism by which it works, and it turns out to be a remarkably sophisticated process. The groups have been able to confirm this mechanism in the laboratory. This work reveals just how powerful these enzymes made of RNA can be, and adds credence to the RNA World idea for the origins of life on the planet. In addition, these species can be used as novel tools in the laboratory and perhaps in medicine and industry. 

Read the full study, published today in Nature Chemical Biology.

Background to this collaboration 

Professor Lilley and Dr Huang have worked together for nearly ten years, beginning when Huang was a postdoctoral researcher in the Lilley lab in Dundee. During this time, they solved the structures of many functional RNA species. Two years ago, Dr Huang moved back to China to a faculty position in Sun Yat-sen University in Guangzhou, and he and Lilley have maintained an active collaboration, sustained by regular Zoom conferences during the pandemic. Prof Lilley has numerous connections with Chinese institutions, being a visiting professor in Xiamen and Nankai universities, and keeping an office in the Chinese Academy Biophysics Institute in Beijing.