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Decoding Functional siRNA: New Approaches

Explore innovative methods for identifying functional siRNA strands by analyzing nucleotide properties and sequence structures. Discover potential gene therapy applications and advancements in RNA interference technology.

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Decoding Functional siRNA: New Approaches

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  1. New approaches for determining functional siRNA Liyang Diao Dr. Stanley Dunn, advisor

  2. mRNA protein DNA Protein Production • Production of proteins starts with DNA • DNA is in the nucleus • Requires mRNA to finish protein production • mRNA: messenger RNA • RNAi: RNA interference • Suppresses gene expression • Affects mRNA http://nobelprize.org/educational_games/medicine/dna/index.html

  3. More on RNAi • siRNA: short-interfering RNA • Typically 20-25 nucleotides long • Double-stranded • Participates in RNAi by degrading mRNA • Potential for effective gene therapy • Issues • Some genes are more effectively suppressed than others • Mechanism is poorly understood Diagram: http://www.ambion.com/techlib/append/RNAi_mechanism.html

  4. Question • How do we know which siRNA are functional? • Some ideal properties: • GC content between 30-55% • Low level of secondary structure • Differential between thermodynamic stability of 5’ and 3’ ends: A/U content • Specific positional nucleotide preferences • Avoid long GC stretches http://bioinf.man.ac.uk/resources/phase/manual/RNAMolecule.png

  5. T A G C Previous Model Pancoska’s Eulerian graph model • Represent a string of siRNA by a directed digraph first • Construct a weighted undirected Eulerian graph • Compare graphs for functional and non functional siRNA • For these two sets of siRNA, compute graph properties that reflect sequence structure.

  6. T A G C Issues with Pancoska’s Algorithm • Uniqueness • Complex pattern recognition Other Ideas • Number of nucleotide mutations • Levenshtein distance: A T T C G T G G A C G G A T T C G T G G A C C G A T T C G T G G A … Measures the minimum number of substitutions/insertions required to go from one string to another.

  7. Current/Future Progress • 420 total number of possible siRNA strands of length 20. • How many are potentially functional? • Combinatorics!

  8. Math • Let H(n,i,j) be the number of potential positions of A/U, G/C pairs. • Thus, the total number of potential strings is 220 * H(n,i,j). • n the total number of G or C nucleotides • i the total number of A or U nucleotides at 5’ end • j the total number of A or U nucleotides at 3’ end Quantity desired:

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