Reduced contact order and RNA folding rates

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• Protein folding rates correlate with relative contact order, reflecting tertiary contact density.
• Unlike proteins, RNA folding typically involves stable secondary structure formation before the rate-limiting step.

Purpose of the Study:

• Investigate the relationship between RNA structure and folding rates, considering hierarchical formation.
• Introduce and validate a new metric, reduced contact order, for RNA folding analysis.
• Classify RNA folding mechanisms based on structural formation kinetics.

Main Methods:

• Calculated reduced contact order for ten different RNAs.
• Correlated folding rates with reduced contact order.
• Compared folding rates of circularly permuted isomers for two distinct RNA classes.

Main Results:

• RNA folding rates and reduced contact order suggest two distinct folding classes.
• Circularly permuted Bacillus subtilis RNase P RNA isomers showed a tenfold variation in folding rates.
• Circularly permuted catalytic domains exhibited only a 1.2-fold variation in folding rates.

Conclusions:

• RNA folding kinetics differ significantly from protein folding.
• The rate-limiting step in RNA folding is influenced by the extent of pre-formed secondary structure.
• Circularly permuted isomer analysis supports the division of RNA folding into distinct mechanistic classes.