SCOL Project: Evolutionary Roles of RNA Aptamers in the Origin of Biological Catalysis
Most of chemical reactions in the current biological systems are catalyzed by enzymes, which can bind, orient and activate the substrates in specific ways. While these functions are highly integrated in enzyme systems, they could be separated as different modules in the prebiotic chemistry. Based on the RNA world hypothesis, RNA evolved first as both genetic information carrier and catalyst before DNA and protein. Therefore, studying the evolutionary roles of RNA in small molecule binding, orientating and activating will provide new insights to explain the origins of biological catalysis as well as certain metabolic networks in the prebiotic chemistry.
The major hypothesis of this project is: small RNA aptamers, which may exist in different variants (such as the hybrid forms of 2’-5’-linked, deoxyribo- and threose linked RNAs), could play important roles by binding substrates with diversified modes, therefore channeling their reactivity towards the most useful products as the potential metabolites. In other words, perhaps early protocells relied on the ambient chemistry for their sources of materials, but simple aptamers, instead of the structurally more complicated ribozymes, helped things along by making the chemistry proceed in a more specific manner, resulting in higher yields of the desired materials, which might facilitate the early metabolisms. Although they might have been inefficient, these aptamers might be able to gradually evolve into a special catalyst of the desired reaction, perhaps by docking into certain relatively nonspecific ribozyme domains and cooperating with other auxiliary domains, similar as the example of ribosome that could evolve by the docking of peptidyl-transferring ribozymes into the protein frames.
In this proposal, we will use phosphorylation, a universal and critical metabolic step in the extant biological systems, as the study model to explore the effects of aptamers in the regioselective phosphorylation of purine and pyrimidine nucleosides, as well as some amino acids, small peptides and other metabolites.
Education: Shanghai Institute of Organic Chemistry, Ph.D., Organic Chemistry
Institution: Research Foundation of SUNY – University at Albany (laboratory of Jia Sheng)