Sprecher
Beschreibung
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. Although this ancestral replicase appears to have been lost, key aspects of RNA-catalyzed RNA replication can be studied “by proxy” with the use of modern RNA enzymes (ribozymes) generated by in vitro selection [1].
We have discovered RNA polymerase ribozymes (RPRs) that are capable of the templated synthesis of another simple ribozyme [2] or long (> 200 nt) RNA oligomers [3] and this activity is potentiated by simple Lys-rich peptides derived from the ribosomal cores [4]. I’ll also be discussing how structured media such as the eutectic phase of water ice [5] - as well as freeze-thaw cycles [6] - may aided early RNA evolution and catalysis and the emergence of functional RNAs from the pools of short RNA oligomers accessible through prebiotic chemistry [7]. More recently we have been engineering triplet polymerase ribozymes that are able to copy and replicate even highly structured RNA templates and enable non-canonical reverse and primer-free replication modes [8].
I’ll be presenting recent progress with the triplet polymerase ribozyme, specifically with respect to the strand separation problem of RNA replication arising from the remarkable stability of RNA duplex intermediates of RNA replication.
References
[1] Wachowius F, Attwater J, Holliger P.(2017) Nucleic acids: function and potential for abiogenesis.
Quarterly Reviews in Biophysics. 50:e4. doi: 10.1017/S0033583517000038. (Review)
[2] Wochner A, Attwater J, Coulson A & Holliger P (2011) Ribozyme-catalyzed transcription of an active ribozyme. Science 332, 209-212
[3] Attwater J, Wochner A & Holliger P (2013) In-ice evolution of RNA polymerase ribozyme activity. Nature Chemistry 5, 1011-1018.
[4] Tagami S, Attwater J, Holliger P. (2017) Simple peptides derived from the ribosomal core potentiate RNA polymerase ribozyme function. Nature Chemistry 9 :325-332
[5] Attwater J, Wochner A, Pinheiro VB, Coulson A & Holliger P (2010) Ice as a protocellular medium for RNA replication. Nature Communications 1, 76.
[6] Mutschler H, Wochner A & Holliger P (2015) Freeze-thaw cycles as drivers of complex ribozyme assembly. Nature Chemistry 7, 502-508.
[7] Mutschler H, Taylor AI, Porebski BT, Lightowlers A, Houlihan G, Abramov M, Herdewijn P, Holliger P. (2018) Random-sequence genetic oligomer pools display an innate potential for ligation and recombination. eLife, 7: e43022
[8] Attwater J, Raguram A, Morgunov AS, Gianni E & Holliger P (2018) Ribozyme-catalysed RNA synthesis using triplet building blocks. eLife, 7: e35255
