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New insights into mechanistic details of co-transcriptional riboswitch regulation

January 2017. Gene repression induced by the formation of transcriptional terminators represents a prime example for the coupling of RNA synthesis, folding and regulation. In this context, mapping the changes in available conformational space of transcription intermediates during RNA synthesis is important to understand riboswitch function. A majority of riboswitches, an important class of small metabolite-sensing regulatory RNAs, act as transcriptional regulators, but the dependence of ligand binding and the subsequent allosteric conformational switch on mRNA transcript length has not yet been investigated. A team of scientists from Frankfurt and Vienna were able to show a strict fine-tuning of binding and sequence-dependent alterations of conformational space by structural analysis of all relevant transcription intermediates at single nucleotide resolution for the I-A type 2’dG-sensing riboswitch from the microorganism Mesoplasma florum by NMR spectroscopy. Their results provide a general framework to dissect the coupling of synthesis and folding essential for riboswitch function, revealing the importance of metastable states for RNA-based gene regulation. More ...

 

Contact:
Harald Schwalbe, Institute of organic Chemistry and chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Campus Riedberg, Goethe University Frankfurt, Frankfurt/Main, Germany, schwalbe@nmr.uni-frankfurt.de

Reference:
Helmling C, Wacker A, Wolfinger MT, Hofacker IL, Hengesbach M, Fuertig B, Schwalbe H (2017) NMR structural profiling of transcriptional intermediates reveals riboswitch regulation by metastable RNA conformations. J Am Chem Soc: published online 30 January 2017. http://dx.doi.org/10.1021/jacs.6b10429