Compact intermediates in RNA folding
Annual Reviews in Biophysics
Sarah A. Woodson
T. C. Jenkins Department of Biophysics, Johns Hopkins University, 3400 N. Charles St.,
Baltimore, MD 21218 USA
tel. 410-516-2015
FAX 410-516-2015
swoodson@jhu.edu
Running title: RNA folding pathways
Keywords: ribozyme, energy landscape, collapse transition, SAXS, single-molecule FRET,
hydroxyl radical footprinting

2Abstract:
Large non-coding RNAs fold into their biologically functional structures via compact yet
disordered intermediates, which couple the stable secondary structure of the RNA with the
emerging tertiary folding. The specificity of the collapse transition, which coincides with the
assembly of helical domains, depends on RNA sequence and counterions. It determines the
specificity of the folding pathways and the magnitude of the free energy barriers to the ensuing
search for the native conformation. By coupling helix assembly with nascent 3D interactions,
compact folding intermediates in RNA also play a crucial role in ligand and protein recognition.
INTRODUCTION ......................................................................................................................3
STRUCTURAL HIERARCHY IN RNA.....................................................................................3
Folding Energetics 3
Timescales for RNA folding 5
KINETIC PARTITIONING OF FOLDING PATHWAYS..........................................................6
Experimental evidence for kinetic partitioning 7
Pathway diversity in small RNAs 7
COLLAPSED STATES IN RNA................................................................................................8
Tertiary interactions direct helix assembly 9
Specificity of collapse 10
Counterion charge density and compact states of RNA 11
SEARCH FOR THE NATIVE STRUCTURE...........................................................................13
Helix docking and induced fit 13
Slow refolding of the group I ribozyme core 14
Local conformational change in RNase P C-domain 15
Folding barriers in group II ribozymes 16
PROSPECTS FOR RNA BIOLOGY ........................................................................................18
ACKNOWLEDGEMENTS ......................................................................................................19
REFERENCES .........................................................................................................................19