Selection of self-replicating ribozymes

Whitehead Institute For Biomedical Res, Cambridge MA

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Abstract

DESCRIPTION (provided by applicant): The broad, long-term objective of the proposed research is to generate and study a self-replicating and evolving system of catalytic RNAs (ribozymes). The scope of the proposed research is to improve the central catalytic activity in such a system, a polymerase activity. Its polymerization efficiency is limited by its weak substrate affinity. To improve the substrate interactions, two strategies will be used: 1) Optimize the ribozyme's substrate affinity by in vitro selection 2) Co-localize ribozyme and substrate on a hydrophobic surface by hydrophobic anchors. If the catalytic efficiency can be improved sufficiently, it will help to generate a self-replicating and evolving system. The hydrophobic interactions (aim 2) could be used to link encoded ribozymes (phenotype) with ribozyme-encoding templates (genotype). If hydrophobic units such as micelles are used, this is a simple way for compartmentalization that might be sufficient for genotype-phenotype linkage in a self-replicating and evolving system. The study of such a system could help to understand the behavior of the much larger networks in contemporary biology as well as possible steps in the origin of life.