Abstract
The emergence of an RNA molecule capable of replicating itself and other RNA sequences is a central pillar of hypotheses regarding the origin of life1,2. In vitro evolution has yielded polymerase ribozymes (PR) that can copy a range of RNA templates using nucleotide3-10 or trinucleotide triphosphates (triplets)11 as substrates and may give rise to a replicase activity. However, our understanding of PR function is encumbered by a lack of structural information beyond the progenitor class I ligase (cIL) ribozyme12-14. Here, we report the structure of the complete 5TU+t1 triplet polymerase ribozyme (TPR) apoenzyme and map its structure / function landscape. The TPR is an RNA heterodimer, comprising a catalytic (5TU) and a catalytically inactive (t1) subunit held together by two kissing loop interactions and its overall structure resembles a left hand with thumb and fingers at a 70° angle. While the 5TU subunit shows partial structural homology to the cIL, the t1 accessory subunit - despite sharing the same progenitor - exhibits a dramatically reorganized secondary and tertiary structure. Our combined structural and functional data suggest a model for templated RNA synthesis by the TPR holoenzyme and provide a foundation for a better understanding of RNA’s potential for self-replication.
Competing Interest Statement
The authors have declared no competing interest.