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Short interfering RNA siRNA

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Presentation on theme: "Short interfering RNA siRNA"— Presentation transcript:

1 Short interfering RNA siRNA
11/27/2018

2 Part I: Gene silencing exist in many multicellular organisms
fruitfly Drosophila roundworm C. elegans fungus Neurospora 11/27/2018

3 Gene silencing go back to the earliest epochs of life on Earth
Wang, Kumar & Hedges, 1999 This ancient immune system seems conserved over 1.5 billion years ...thus we can learn about different aspects of gene and RNA silencing wherever it is easiest... plants... roundworms... flies human cell lines... 11/27/2018

4 A brief history of RNA silencing
1998: Andrew Fire and colleagues show that double-stranded RNA induce gene silencing in C. elegans 1999: Hamilton & Baulcombe find small RNA where genes are silenced in plants 2000: Greg Hannon and colleagues isolate Dicer, the siRNA producing RNase-III enzyme in Drosophila 2001: Thomas Tuschl and colleagues show that synthetic small RNA introduced into human cells can silence human genes 11/27/2018

5 13.10 RNA Interference Is Related to Gene Silencing
RNA interference triggers degradation of mRNAs complementary to either strand of a short dsRNA. 11/27/2018 Figure 13.21

6 Model for RNAi mechanism
Dicer (RNA-induced silencing complex) Initiation step Effector step 11/27/2018 Hammond et al., 2001

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9 Produzione di siRNA Brummelkamp, 2002; Paddision, 2002; Miyahishi, 2002; Paul, 2002; Sui, 2002; Lee, 2002; Jacque, 2002; Yu, 2002; Yang, 2002 11/27/2018

10 Inhibition of cholesterol synthesis by siRNA: A recent study by Alnylam Inc
"...Administration of chemically modified siRNAs resulted in silencing of the apoB messenger RNA in liver and jejunum, decreased plasma levels of apoB protein, and reduced total cholesterol. " Soutschek et al, Nature, 2004 11/27/2018

11 More small RNA exist stRNA (short temporal RNA, also called micro-RNA, miRNA) inhibit mRNA translation (Lee & Ambros, 1993; Reinhart, 2000; Lee, 2001; Lau, 2001; Lagos-Quintana, 2001; Llave, 2002; Lim, 2003) microRNA comes from microGenes, transcripted as ~70 nt hairpins, and processed (as is shRNA) to short ~21-mer RNAs... 11/27/2018

12 13.9 MicroRNAs Are Regulators in Many Eukaryotes
Animal and plant genomes code for many short (~22 base) RNA molecules called microRNAs. MicroRNAs regulate gene expression by base pairing with complementary sequences in target mRNAs. 11/27/2018

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