Replicating RNA with RNAGroup Leader Page
A critical event in the origin of life is thought to have been the emergence of an RNA molecule capable of self-replication as well as mutation, and hence evolution towards ever more efficient replication.
The Holliger lab uses synthetic biology approaches to reconstruct modern day equivalents of the ancestral replicase and study life’s first genetic system “by proxy” with the use of modern-day RNA enzymes (ribozymes) generated by in vitro evolution. Progress in this area has fundamental implications for a better understanding of both the origin of life and the engineering of simple chemical systems with life-like properties.
Previously we have discovered RNA polymerase ribozymes that are capable of the templated synthesis of another simple ribozyme (Wochner et al, 2011) or long (> 200 nt) RNA oligomers and this activity is potentiated by structured media such as the eutectic phase of water ice (Attwater et al, 2010, 2013) and by simple peptides derived from the cores of both ribosomal subunits (Tagami et al, 2017). More recently, we have discovered triplet polymerase ribozymes that are for the first time able to replicate highly structured RNAs like themselves Triplet-based RNA replication also enables non-canonical primer-free and reverse direction (3’-5’) modes of RNA replication not seen in nature and revealed unexpected systems-level properties of the triplet substrate pools that enhance replication fidelity (Attwater et al, 2018).
Potential projects will focus on advancing RNA-catalyzed RNA synthesis towards a system capable of self-replication and evolution.
Wochner, A., Attwater, J., Coulson, A. and Holliger, P (2011)
Ribozyme-catalyzed transcription of an active ribozyme.
Attwater J, Wochner A & Holliger P (2013)
In-ice evolution of RNA polymerase ribozyme activity.
Nature Chemistry 5:1011-1018.
Attwater J, Wochner A, Pinheiro VB, Coulson A & Holliger P (2010)
Ice as a protocellular medium for RNA replication.
Nature Communications 1:76.
Tagami S, Attwater J, Holliger P. (2017)
Simple peptides derived from the ribosomal core potentiate RNA polymerase ribozyme function.
Nature Chemistry 9:325-332
Attwater J., Raguram A., Morgunov A.S., Gianni E. & Holliger P. (2018)
Ribozyme-catalysed RNA synthesis using triplet building blocks.