TY  - JOUR
A1  - Knežić, Božana
A1  - Keyhani, Sara
A1  - Schwalbe, Harald
T1  - Mapping the conformational landscape of the neutral network of RNA sequences that connect two functional distinctly different ribozymes
T2  - ChemBioChem
N2  - During evolution of an RNA world, the development of enzymatic function was essential. Such enzymatic function was linked to RNA sequences capable of adopting specific RNA folds that possess catalytic pockets to promote catalysis. Within this primordial RNA world, initially evolved self-replicating ribozymes presumably mutated to ribozymes with new functions. Schultes and Bartel (Science 2000, 289, 448–452) investigated such conversion from one ribozyme to a new ribozyme with distinctly different catalytic functions. Within a neutral network that linked these two prototype ribozymes, a single RNA chain could be identified that exhibited both enzymatic functions. As commented by Schultes and Bartel, this system possessing one sequence with two enzymatic functions serves as a paradigm for an evolutionary system that allows neutral drifts by stepwise mutation from one ribozyme into a different ribozyme without loss of intermittent function. Here, we investigated this complex functional diversification of ancestral ribozymes by analyzing several RNA sequences within this neutral network between two ribozymes with class III ligase activity and with self-cleavage reactivity. We utilized rapid RNA sample preparation for NMR spectroscopic studies together with SHAPE analysis and in-line probing to characterize secondary structure changes within the neutral network. Our investigations allowed delineation of the secondary structure space and by comparison with the previously determined catalytic function allowed correlation of the structure-function relation of ribozyme function in this neutral network.
KW  - analytical chemistry
KW  - NMR spectroscopy
KW  - ribozymes
KW  - RNA structures
KW  - SHAPE analysis
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/75430
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-754309
SN  - 1439-7633
N1  - We acknowledge the DFG for financial support through GRK 1986 “CLiC”. Work at BMRZ was supported by the state of Hesse. Open Access funding enabled and organized by Projekt DEAL.
VL  - 23
IS  - 7, art. e202200022
SP  - 1
EP  - 8
PB  - Wiley-VCH
CY  - Weinheim
ER  -