Gene silencing by siRNA:zipper_mouth_face::
Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA molecules, 20-25 base pairs in length, similar to miRNA, and operating within the RNA interference (RNAi) pathway. It interferes with the expression of specific genes with complementary nucleotide sequences by degrading mRNA after transcription, preventing translation.
The mechanism by which siRNA causes gene silencing through repression of transcription occurs as follows:
- Long dsRNA (which can come from hairpin, complementary RNAs, and RNA-dependent RNA polymerases) is cleaved by an endo-ribonuclease called Dicer. Dicer cuts the long dsRNA to form short interfering RNA or siRNA; this is what enables the molecules to form the RNA-Induced Silencing Complex (RISC).
- Once siRNA enters the cell it gets incorporated into other proteins to form the RISC.
- Once the siRNA is part of the RISC complex, the siRNA is unwound to form single stranded siRNA.
4.The strand that is thermodynamically less stable due to its base pairing at the 5´end is chosen to remain part of the RISC-complex
- The single stranded siRNA which is part of the RISC complex now can scan and find a complementary mRNA
- Once the single stranded siRNA (part of the RISC complex) binds to its target mRNA, it induces mRNA cleavage.
7.The mRNA is now cut and recognized as abnormal by the cell. This causes degradation of the mRNA and in turn no translation of the mRNA into amino acids and then proteins. Thus silencing the gene that encodes that mRNA.
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