Question

Explain how microRNAs lead to the degradation of targeted mRNAs. In your explanation, state the role of DICER and of RISCs ( RNA-induced silencing complexes). Explain how siRNAs, DICER, and RISCs function to protect cells from infection by dsDNA viruses.

Answer 1

The microRNA s are very small ( around 22 nucleotides) non coding RNA. MicroRNA are transcribed by RNA polymerase II which generates pri-miRNA transcript which is generally 60-70 nucleotide long. Pri-mRNA is further processed by an enzyme Drosha to produce a hairpin loop structure known as pre-miRNA. pre-miRNA is then transported to nuclus by exportin V and Ran-GTP cofactor, and then enzyme dicer cleaved pre-miRNA and produce   miRNA/miRNA duplexes.   Dicer processing is also though to produce unwinding of the duplex. Single stranded miRNA then forms a complex with RNA-induced silencing complex (RISC). miRNA in a complex with RISC then bind to mRNA and inhibit or degrade mRNA.

RNAi or RNA interference is a biological proecess where RNA molecules can inhibit gene expression by inihbiting the effect of mRNA. siRNA can defend cell against viral infection. The siRNA pathway is initiated by enzyme Dicer which cleaves double stranded RNA into small fragments of siRNA. Each fragments then unwind to generate single stranded RNA - a passanger strand and a guide strand. The passanger strand is further degraded and guide strand is formed a complex with RNA-induced silencing complex (RISC). The siRNA-RISC complex next paired with complementary strand of mRNA and cleavage of mRNA is initiated by Argonaute 2 which is catalytic componenet of RISC complex.