Research Article

Processive RNA polymerization and promoter recognition in an RNA World

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Science  19 Mar 2021:
Vol. 371, Issue 6535, pp. 1225-1232
DOI: 10.1126/science.abd9191

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A processive RNA replicator

The RNA World Hypothesis suggests that, before modern life, there were RNA molecules that were capable of carrying genetic information and driving chemical reactions, a task gradually replaced by DNA and enzymes in modern biology. Central to this theory is an RNA replicase capable of mediating general replication of RNA. Using laboratory evolution, Cojocaru et al. isolated a promoter-based RNA polymerase ribozyme that, analogous to modern-day protein polymerases, clamps onto templates to increase its processivity, making it a potential model for replication in early biology.

Science, this issue p. 1225


Early life is thought to have required the self-replication of RNA by RNA replicases. However, how such replicases evolved and subsequently enabled gene expression remains largely unexplored. We engineered and selected a holopolymerase ribozyme that uses a sigma factor–like specificity primer to first recognize an RNA promoter sequence and then, in a second step, rearrange to a processive elongation form. Using its own sequence, the polymerase can also program itself to polymerize from certain RNA promoters and not others. This selective promoter–based polymerization could allow an RNA replicase ribozyme to define “self” from “nonself,” an important development for the avoidance of replicative parasites. Moreover, the clamp-like mechanism of this polymerase could eventually enable strand invasion, a critical requirement for replication in the early evolution of life.

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