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Class 5: RNA Structure Prediction

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Title: Class 5: RNA Structure Prediction


1
Class 5RNA Structure Prediction
2
RNA types
  • Messenger RNA (mRNA)
  • Encodes protein sequences
  • Transfer RNA (tRNA)
  • Adaptor between mRNA molecules and amino-acids
    (protein building blocks)
  • Ribosomal RNA (rRNA)
  • Part of the ribosome, a machine for translating
    mRNA to proteins
  • mi-RNA (micro-)
  • Sn-RNA (small nuclear)
  • RNA-I (interfering)
  • Srp-RNA (Signal Recognition Particle)

3
Functions of RNAs
Information Transfer mRNA
Codon -gt Amino Acid adapter tRNA
Other base pairing functions ???
Enzymatic Reactions
Structural
Metabolic ???
Regulatory RNAi
4
RNA World Hypothesis
  • Before the invention of DNA and protein, early
    organisms relied on RNA for both genetic and
    enzymatic processes
  • DNA was a selective advantage because it greatly
    enhanced the fidelity of genetic replication
  • Proteins were a selective advantage because they
    make much more efficient enzymes
  • Remnants of the RNA world remain today in
    catalytic RNAs in ribosomes, polymereases and
    slicing molecules

5
Why is RNA structure important?
  • Messenger RNA is a linear, unstructured sequence,
    encoding an amino-acid sequence
  • Most non-coding RNAs adopt 3D structures and
    catalyse bio-chemical reactions.
  • Predicting structure of a new RNA gt information
    about its function

6
Terminology of RNA structure
  • RNA a polymer of four different nucleotide
    subunits
  • adenine (A) , cytosine (C), guanine (G)and
    uracil (U)
  • Unlike DNA, RNA is a single stranded molecule
    folding intra-molecularly to form secondary
    structures.
  • RNA secondary structure set of base pairings in
    the three dimensional structure of the molecule
  • G-C has 3 hydrogen bonds
  • A-U has 2 hydrogen bonds
  • Base pairs are almost always stacked onto other
    pairs, creating stems.

7
Base Pairing in RNA
guanine
cytosine
adenine
uracil
8
Non-canonical pairs and pseudoknots
  • In addition to A-U and G-C pairs, non-canonical
    pairs also occur. Most common one is G-U pair.
  • G-U is thermodynamically favourable as
    Watson-Crick pairs (A-U, G-C) .
  • Base pairs almost always occur in nested fashion.
    Exception pseudoknots.

9
Elements of RNA secondary structure
10
RNA Secondary Structure(more)
11
(No Transcript)
12
RNA Tertiary Structure
  • Do not obey parantheses rule

13
tRNA structure
14
Structure vs Sequence
  • Homologous RNAs that have common secondary
    structure without sharing significant sequence
    similarity are important.
  • It is advantageous to search conserved secondary
    structure in addition to conserved sequence in
    databases.

15
Example R17 phage coat protein
Durbin, p. 264
16
Two Problems
  • RNA secondary structure for a single sequence.
    The dynamic programming algorithms Nussinov
    and Zuker, SCFG algorithms.
  • Analysis of multiple alignments of families of
    RNAs.
  • Covariance Models used for both multiple
    alignment and database searches.

17
Problem I Structure Prediction
  • Input An RNA sequence X
  • Output Most likely secondary structure of X
  • Algorithms Nussinov, CYK, MFOLD,

18
Problem II RNA family modeling
  • Input A family for RNA sequence X1, , XN
    sharing a common secondary structure
  • Aligned / Not aligned
  • Output A probabilistic generative model
    representing the RNA family
  • Model Covariance model
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