Predicting higher-order mutational effects in an RNA enzyme by machine learning of high-throughput experimental data.

ABSTRACT: Ribozymes are RNA molecules that catalyze biochemical reactions. Self-cleaving ribozymes are a common naturally occurring class of ribozymes that catalyze site-specific cleavage of their own phosphodiester backbone. In addition to their natural functions, self-cleaving ribozymes have been used to engineer control of gene expression because they can be designed to alter RNA processing and stability. However, the rational design of ribozyme activity remains challenging, and many ribozyme-based systems are engineered or improved by random mutagenesis and selection (in vitro evolution). Improving a ribozyme-based system often requires several mutations to achieve the desired function, but extensive pairwise and higher-order epistasis prevent a simple prediction of the effect of multiple

SUBMITTER: Beck JD 

PROVIDER: S-EPMC9421044 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature