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A turbo intro to (the bioinformatics of) microRNAs 11/6 2009 Peter Hagedorn

A turbo intro to (the bioinformatics of) microRNAs 11/6 2009 Peter Hagedorn. Discovery of microRNA. The first described microRNA , lin-4 , was cloned and characterised as a translational repressor of developmental timing from C. elegans by Lee et al (1993) and Wightman et al (1993).

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A turbo intro to (the bioinformatics of) microRNAs 11/6 2009 Peter Hagedorn

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  1. A turbo intro to (the bioinformatics of) microRNAs11/6 2009Peter Hagedorn

  2. Discovery of microRNA • The first described microRNA, lin-4, was cloned and characterised as a translational repressor of developmental timing from C. elegans by Lee et al (1993) and Wightman et al (1993). • The transcript of this gene was highly unusual as it was non-coding, and produced extremely small transcripts (22nt) from hairpin structured RNA precursors. • Second microRNA, let-7, was also cloned from C. elegans(Reinhart et al, 2000).

  3. microRNA research Drugs againstmicroRNAstestedin monkeys 1600 1400 1200 1000 800 600 400 200 0 microRNAsdiscoveredin human, mice, and Drosophila microRNAsidentifiedin viralgenomes Number of publications microRNAsimplicatedin leukemia 2001 2002 2003 2004 2005 2006 2007 2008 Time (year)

  4. microRNAstatistics • Probably >1000 miRNAs in mammaliangenomesIdentifiedpresently (March 2009) - 706 human miRNAs - 547 mousemiRNAs - 286 rat miRNAs • May modulate the expression of at least30% of all protein coding genes in a genome • ~60% of miRNAsareexpressedindependently~15% areencoded in clusters~25% arefound in introns HOXD4 homeobox D4 DLEU2 deleted in lymphocytic leukemia 2 (non-protein coding) MIRHG2 microRNA host gene 2 (non-protein coding) • Manyarehighlyconserved

  5. microRNAsynthesis

  6. MicroRNA-mRNAinteraction 5´ 3´ 3´ 5´

  7. microRNAfunction

  8. microRNAfunction

  9. microRNAstargeting 3’UTRs Systematic discovery of regulatory motifs in human promoters and 3' UTRs by comparison of several mammals (Xie et al., 2005)

  10. microRNAstargeting CDS A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence (Forman et al., 2008)

  11. microRNAtargetprediction

  12. Seed conservation

  13. microRNAstargetspecificprocesses

  14. microRNAregulatoryprinciples

  15. microRNAsilencing

  16. microRNAoverexpression pri-miRNA

  17. Cross-linking immunoprecipitation coupled with high-throughput sequencing (CLIP-seq)

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