RNA quadruplex folding and stabilisation by metal ion complexes on the single molecule level

• Research unit: COST
• Project number: C12.0112

Key words (English)

G-quadruplex; RNA; NRAS; TERR2; smFRET; single molecule; proto-oncogene; metal complex

Research programs (English)

COST-Action CM1105 - Functional metal complexes that bind to biomolecules

Short description (English)

See abstract

Partners and International Organizations (English)

AT; HR; CZ; DK; FI; FR; DE; EL; HU; IS; IE; IL; IT; NL; PL; PT; RO; SI; ES; RS; CH; SE; TR; UK

Abstract (English)

The COST Action CM1105 focuses on the development of novel metallo-drugs in a structure-targeted approach. Our contributions to the aims of this Action are directed towards understanding the thermodynamic, kinetic and structural details of the molecular interaction between the metallo-drugs and their biomolecular targets, i.e., specifically complex RNA structures. Here we focus on RNA quadruplex structures, which predominantly occur in regulatory regions on the mRNA level in vivo. In contrast to their DNA equivalents, only very little is known on their structure, folding, metal ion requirement and general behavior. During this project we have focused to established a system, which is structurally uniform and well characterized: We have (i) characterized the metal ion selectivity of two different RNA quadruplexes, (ii) understood the structural equilibrium of an oncogenic quadruplex and isolated two constructs of the two major forms, (iii) made considerable progress on the NMR structure determination of a third sequence, (iv) developed in collaboration a sequence-specific labeling scheme for long RNAs, (v) measured first single molecule FRET experiments with these constructs, and (vi) characterized in detail the interaction of a metal ion complex with a quadruplex by fluorescence spectroscopy.

References in databases (English)

Swiss Database: COST-DB of the State Secretariat for Education and Research Hallwylstrasse 4 CH-3003 Berne, Switzerland Tel. [phone] Swiss Project-Number: C12.0112