TY  - JOUR
A1  - Landgraf, Tom
A1  - Völklein, Albrecht Eduard
A1  - Fürtig, Boris
A1  - Schwalbe, Harald
T1  - The cotranscriptional folding landscape for two cyclic di-nucleotide-sensing riboswitches with highly homologous aptamer domains acting either as ON- or OFF-switches
T2  - Nucleic acids research
N2  - Riboswitches are gene regulatory elements located in untranslated mRNA regions. They bind inducer molecules with high affinity and specificity. Cyclic-di-nucleotide-sensing riboswitches are major regulators of genes for the environment, membranes and motility (GEMM) of bacteria. Up to now, structural probing assays or crystal structures have provided insight into the interaction between cyclic-di-nucleotides and their corresponding riboswitches. ITC analysis, NMR analysis and computational modeling allowed us to gain a detailed understanding of the gene regulation mechanisms for the Cd1 (Clostridium difficile) and for the pilM (Geobacter metallireducens) riboswitches and their respective di-nucleotides c-di-GMP and c-GAMP. Binding capability showed a 25 nucleotide (nt) long window for pilM and a 61 nt window for Cd1. Within this window, binding affinities ranged from 35 μM to 0.25 μM spanning two orders of magnitude for Cd1 and pilM showing a strong dependence on competing riboswitch folds. Experimental results were incorporated into a Markov simulation to further our understanding of the transcriptional folding pathways of riboswitches. Our model showed the ability to predict riboswitch gene regulation and its dependence on transcription speed, pausing and ligand concentration.
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63313
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-633131
SN  - 1362-4962
N1  - Funding: DFG priority program [SPP 1879]; collaborative research center [SFB902]; work at BMRZ is supported by the state of Hesse. Funding for open access charge: institutional funds.
N1  - DATA AVAILABILITY
mFold: http://unafold.rna.albany.edu/?q = mfold
Sedphat: http://www.analyticalultracentrifugation.com/sedphat/download.htm
NITPIC: http://biophysics.swmed.edu/MBR/software.html
Sparky: https://www.cgl.ucsf.edu/home/sparky/
Topspin: https://www.bruker.com/service/support-upgrades/software-downloads/nmr/free-topspin-processing/nmr-topspin-license-for-academia.html.
VL  - 50
IS  - 12
SP  - 6639
EP  - 6655
PB  - Oxford Univ. Press
CY  - Oxford
ER  -