2.1. RNA INTERFERENCE (RNAi) Flashcards
RNAi
- RNA interference
2. Process of sequence-specific (homology-dependent) gene silencing initiated by double-stranded RNA (dsRNA)
miRNA
MicroRNA
Pri-mRNA
- Primary miRNA
2. Large RNA
Monocistronic
Single hairpin loop
Polycistronic
Multiple hairpin loops
Pre-miRNA
Precursor miRNA
Drosha
- dsRNA-binding partner (DGCR8)
- Process Pri-miRNA to pre-miRNA
- Drosha + DGCR8 => microprocessing complex
Exportin-5
XPO5
Dicer
- dsRNA-binding partner TRBP
2. Process pre-miRNA to miRNA duplex
RISC
RNA Induced Silencing Complex
Contains Ago-2
Mature miRNA/ guide
Guides complex to complementary mRNA Wh I his silenced
Perfect match
Silencing occurring through the degradation of mRNA
Imperfect match
Inhibition of translation
Downregulation
Target oncogene
Upregulation
Target a tumor suppressor
dsRNA
Double-stranded RNA initiating RNA interference
What are the two functions of viruses and miRNA?
- Viral miRNA shown to inhibit cellular factors involved in innate/ adaptive immunity
- human cytomegalovirus
- Kaposi’s Sarcoma Associated herpesvirus
- Epstein-Barr virus
• downregulate natural killer cell Logan MICB
• Epstein-Barr virus encoded miRNA also downregulate Pri-apoptotic protein PUMA - Other viral miRNA downregulate expression of viral proteins
- Herpes simplex virus 1 maintains latent state by down-regulating immediate - early trans activators (ICPO & ICP4)