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RNA Secondary Structure

This document discusses RNA secondary structure. It begins by describing the primary structure of RNA which is a sequence of bases A, G, C, and U that can base pair to form A-U and G-C pairs. RNA can fold on itself to form diverse secondary structures stabilized by base pairing. Structures are represented by circular diagrams showing base pairs. There are approximately 1.3 billion possible structures for an RNA sequence of length 27. Common structural elements include hairpin loops, bulge loops, interior loops, junctions, and stacks. Structure prediction methods aim to maximize base pairs or minimize free energy.

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41 views31 pages

RNA Secondary Structure

This document discusses RNA secondary structure. It begins by describing the primary structure of RNA which is a sequence of bases A, G, C, and U that can base pair to form A-U and G-C pairs. RNA can fold on itself to form diverse secondary structures stabilized by base pairing. Structures are represented by circular diagrams showing base pairs. There are approximately 1.3 billion possible structures for an RNA sequence of length 27. Common structural elements include hairpin loops, bulge loops, interior loops, junctions, and stacks. Structure prediction methods aim to maximize base pairs or minimize free energy.

Uploaded by

naiktt
Copyright
© Attribution Non-Commercial (BY-NC)
We take content rights seriously. If you suspect this is your content, claim it here.
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RNA Secondary Structure

Basis of RNA
RNA bases A,C,G,U Primary Structure of RNA : A sequence of the bases A,G,C and U Base Pairs
A-U G-C

non-canonical pairs can occur in RNA -- G-U is the most common

Stability
G-C > A-U > G-U

Basis of RNA
single stranded; strand folds upon itself to form base pairs; can have a diverse form of secondary structure compared to base sequences, structure conservation is most important with RNA

Structure Rules
Base pairing stabilize the structure Unpaired sections (loops) destabilize the structure when a base in one position changes, the base it pairs to must also change to maintain the same structure (covariation)

Representations of Secondary Structure


Most basepairs are non-crossing basepairs: Any two pairs (i, j) and (i,j) i < i < j < j or i < i < j < j

Circular Representation of Base Pairs


base pairs of a secondary structure represented by a circle arc drawn for each base pairing in the structure

Circular Representation of Base Pairs

RNA Combinatorics
The number of RNA secondary structures for the sequence [1,n]

s (0) = s(1) = s (2 ) = 1 s (n + 1) = s(n ) + s( j 1)s(n j ), (n 2 )


j =1 n 1

Recurrence Relation

based on the combinatorics, there are approximately 1.3 billion possible RNA structures of length n = 27.

Types of different regions in RNA secondary structure

Hairpin Loop
generally at least 4 bases long for each loop

Bulge Loops
occur when bases on one side of the structure cannot form base pairs

Interior Loops
occur when bases on both sides of the structure cannot form base pairs

Junctions (Multi-loops)
two or more double-stranded regions converge to form a closed structure

RNA Secondary Structure

Stacks: continuous nested basepairs. (energetically favorable) Non-basepaired loops:


Hairpin loop. Bulge. Internal loop. Multiloop.

RNA structure prediction methods


Maximize Base Pairs Minimize Energy

Maximize Base Pairs


Given a RNA sequence, determine the set of maximal basepairs(no basepair across each other) Align bases according to their ability to pair with each other gives an approach to determining the optimal structure dynamic programming approach Nussinov Algorithm

Nussinov Algorithm
Four ways to get the optimal structure between position i and j from the optimal substructure

Nussinov Algorithm
compares a sequence against itself in a n*n matrix Find the maximum of the scores for the four possible structures at a particular position

Nussinov Algorithm
this method will not necessarily generate the most stable structure may have scattered matches which are not biologically reasonable Does not give accurate structure predictions

Minimize Energy
All possible choices of complementary sequences are considered
consider all possible choices of complementary sequences to find the most stable structure Stacks (contiguous nested base pairs) are the dominant stabilizing force contribute to the negative free energy Unpaired bases form destabilizing loops, contributing the positive free energy.
Hairpin loops, bulge/internal loops, and multiloops.

Uses Dynamic Programming alignment technique

Minimize Energy
Energy minimization algorithm predicts the secondary structure by minimizing the free energy (G) G calculated as sum of individual contributions of:
loops base pairs secondary structure elements

Free-energy values (kcal/mole at 37oC )

Free-energy values (kcal/mole at 37oC )

Given the energy tables, the free energy can be calculated for a structure

The score in dynamic programming is based on the free energy values Gaps represent some form of a loop The most widely used software that incorporates this minimum free energy algorithm is MFOLD/RNAfold

Drawbacks
Only have one optimal solution

Features from secondary structure


Prediction of Mammalian MicroRNA Targets, Benjamin P. Lewis etc. Assumption:
Perfect Watson-Crick complementarity to bases 28 of the miRNA extend each seed match to a longer target site

The miRNA/target site duplex stability was evaluated by assigning energy (G) to the duplex
A candidate target site was rejected if the G value was higher than a threshold

Features from secondary structure


Nave Bayes for MicroRNA Target Predictions- Machine Learning for MicroRNA Targets, Malik Yousef etc. Assumption:
A seed segment with weak complementarity can be compensated for by the out-seed sequence

partition the duplex into two parts, the seed (8nt of the miRNA) and out-seed For each part, consider the following feature of the duplex
The number of paired bases the number of bulges the number of loops the number of asymmetric loops eight features, each representing the number of bulges of lengths 1-7 and those with lengths greater than 7

Eight features, each representing the number of symmetric loops with lengths 1-7 and those with lengths greater than 7. Eight features each representing the number of asymmetric loops with lengths 1-7 and those with lengths greater than 7. the distance from the start of the seed (the 3 end) to the first paired base of the 5 start of the out-seed

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