Software Tools :: RNA Secondary Structure Analysis
In the cell, single-stranded RNA molecules fold to form complex
two-dimensional structures. The basic structural unit is a
double-stranded helix, formed by hydrogen bonding between G-C, A-T, and
G-U base pairs. Helical regions may be disrupted by the occurrence of
one or a few non-hydrogen-bonded bases, causing bulges, or by longer
stretches of single-stranded regions, forming loops. Single-stranded
dangling ends occur if the ends of the molecule do not participate in
hydrogen bonding. The two-dimensional folding patterns form the skeleton
for the overall three-dimensional structure of the molecule.
Determining the secondary structure of an RNA molecule can be an
important clue to understanding its regulation and function. In the case
of pre-mRNAs and mature mRNAs, secondary structure elements can act as
regulatory signals for intron-splicing, translation initiation,
transcriptional pauses, and transcriptional attenuation in
bacterial operons. The secondary structure of tRNAs and rRNAs is
important for the assembly and function of these molecules. For all types
of RNA, the secondary structure can determine the subcellular location
of the molecule and its stability.
Fortunately, the factors determining the folding patterns of RNAs are
simpler than those involved in folding proteins. Current
state-of-the-art programs for predicting RNA secondary structure are
based on the following assumptions:
- an RNA molecule folds to form the structure of minimum free
energy
- the minimum free energy of the molecule as a whole can
be calculated from the sum of independent contributions of each of its
elementary structural motifs (Tinoco-Uhlenbeck postulate)
- the energies to be measured consist of hydrogen-binding energies
and base-stacking energies in the double-stranded regions, offset by
the destabilizing effects of intervening single-stranded regions
Crystallography and NMR structure determination methods show that
these assumptions are realistic for the folding of short RNAs, but are
too simplistic for longer RNAs, where the biologically correct structure
may not be the energetically optimal one. Suboptimal structures can be
stabilized in vivo by factors that the current algorithms cannot
account for: long-range interactions within the molecule (pseudoknots),
interactions with ions in solution, and interactions with other RNAs or
with proteins. However, empirical studies have shown that the correct
structure is often within a few percent of the calculated minimum
energy. The best prediction programs, such as Michael Zuker's mfold,
calculate suboptimal secondary structure patterns in addition to the optimal
one.
Back to RNA
Secondary Structure Analysis
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