MiRNAs Cancer Gravesnmo

MiRNAs Cancer Gravesnmo - MicroRNAs in Cancer Click to edit...

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Click to edit Master subtitle style MicroRNAs in Cancer Paul Graves, Ph.D. Virginia Commonwealth University
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Overview • Background • microRNAs in cancer • Regulation of microRNAs?
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Background
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Central Dogma of Biology: DNA RNA Protein transfer RNA ribosomal RNA “Coding” small nuclear RNA “Non-coding
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DNA RNA Protein “Coding” “RNA interference” Small interfering RNA (non-coding)
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Where does the small interfering RNA come from? It comes from us- it is in our genome!
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Click to edit Master subtitle style Percent of DNA not coding for proteins Most of our DNA does not code for proteins! Only ~2% of our DNA codes for proteins!! What is the rest of the DNA (98%) for?
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Click to edit Master subtitle style However… …it must be “Junk” DNA right? “Genetic junk left over during evolution”
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Click to edit Master subtitle style 1) Most of the “junk” DNA is transcribed… 60-70% actually… 2) Much of the “junk” DNA has been conserved throughout evolution Suggests it is important…
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DNA Interfering RNA (non- coding) What does it do? What is it?
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• small interfering RNA • microRNA • short hairpin RNA Many types of non-coding RNA • piwi RNA
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Types of small RNAs 1. siRNA (small interfering RNA) 2. miRNA (microRNA) • not widely present in animal cells • usually artificially introduced to cells • expressed by an organism’s genome
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Biogenesis of microRNAs and siRNAs Several thousand nucleotides 60-100 nucleotides 19-22 nucleotides * * * = can be artificially introduced
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How does siRNA or miRNA work? 1. Messenger RNA degradation 2. Inhibition of protein translation -yes, do kill the messenger!
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Click to edit Master subtitle style siRNA and miRNAs function differently 2. miRNAs 5 AAAAA A Ag o siRN A mRN A 5 RNA cleavage 5 AAAA AA A g o miR NA mR NA 5 1. siRNAs
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RNAi-the movie Coming to a theater near you!
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The first miRNA Lee et al., (1993) Cell ; Wightman et al., (1993) Cell AAA A UUC-UAC------- CUCAGGGAAC 3’--UGAGUGUGAACUCCAGAGUCCCUUG-- 5’ 3’ UTR (untranslated region) lin- 4 • Nobel Prize in Medicine (2006)- Andrew Fire and Craig Mellow Discovered in roundworms,C. elegans, (1993). 3 5 5 lin-14 mRNA miRNA
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Genomic Organization of  Zhao Y, Srivastava D, TIBS 32:189,2007 At least 50% of miRNAs originate from intronic regions
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MicroRNAs by the numbers • One miRNA may target up multiple mRNAs • One mRNA may have multiple miRNA binding sites • ~30% of all human genes are targets of miRNA • Number human miRNAs identified: ~700
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Click to edit Master subtitle style miRNAs and their targets:
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miRNA nomenclature mir-223: pre-miRNA miR-223: mature form miR-146a
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MiRNAs Cancer Gravesnmo - MicroRNAs in Cancer Click to edit...

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