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Probing complex RNA structures by mechanical force (2003)

Abstract
RNA secondary structures of increasing complexity are probed combining single molecule stretching experiments and stochastic unfolding/refolding simulations. We find that force-induced unfolding pathways cannot usually be interpretated by solely invoking successive openings of native helices. Indeed, typical force-extension responses of complex RNA molecules are largely shaped by stretching-induced, long-lived intermediates including non-native helices. This is first shown for a set of generic structural motifs found in larger RNA structures, and then for Escherichia coli's 1540-base long 16S ribosomal RNA, which exhibits a surprisingly well-structured and reproducible unfolding pathway under mechanical stretching. Using out-of-equilibrium stochastic simulations, we demonstrate that these experimental results reflect the slow relaxation of RNA structural rearrangements. Hence, micromanipulations of single RNA molecules probe both their native structures and long-lived intermediates, so-called "kinetic traps", thereby capturing -at the single molecular level- the hallmark of RNA folding/unfolding dynamics.

Publication details
Download http://hal.archives-ouvertes.fr/hal-00000601/en/
Publisher HAL - CCSD
Repository CCSd/HAL : e-articles server (based on gBUS) (France)
Keywords Physics/Physics/Biological Physics, RNA folding/unfolding, Single molecule experiments, Stochastic simulations, Non-native helices and kinetic traps, 16S ribosomal RNA
Type peer-reviewed article
Language English
Relation http://hal.archives-ouvertes.fr/docs/00/00/06/01/PDF/pullingrna_2C.pdf

Cited publications (3)
Modeling RNA folding paths with pseudoknots: Application to hepatitis delta virus ribozyme
RNA Movies - Visualizing RNA Secondary Structure Spaces (1997)
On the simulation of protein folding by short time scale molecular dynamics and distributed computing