RNA interference (RNAi) is a biological process in which RNA molecules silence specific genes, it's first discovered in plants and Caenorhabditis elegans and later in mammalian cells. This discovery is one of the most important advances in biology, so Andrew Fire and Craig C. Mello shared the 2006 Nobel Prize in Physiology or Medicine for their contribution on discovery of RNAi technology. RNAi technology is becoming an important tool for cancer research nowadays.
There are two effector molecules involving RNAi, one is small interfering RNA (siRNA for short), the other is micro RNA (miRNA for short).
siRNA is a class of small (20-30 nucleotides), double stranded, non-coding RNA molecules. siRNA regulates eukaryotic gene expression at the most important levels of genome function, including chromosome segregation, chromatin structure, RNA processing, RNA stability, transcription, and translation.
The mechanism of gene silencing by siRNA is as follows
- Long double stranded RNA (dsRNA) is cleaved by an RNase III-like enzyme named Dicer. Dicer cuts the long dsRNA to form siRNA.
- The active antisense strand is loaded into a protein complex called the RNA-induced silencing complex (RISC).
- siRNA-RISC complex guides the recognition of complementary mRNAs.
- siRNA-RISC complex binds to its target sequence of mRNA, and the mRNA is cleaved by Argonaute 2 (Ago) of the RISC, and then degraded, resulting in reduced protein expression from the silenced gene.
Figure 1. RNAi Mechanism using siRNA
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- Ahmadzada T, Reid G, McKenzie DR. Fundamentals of siRNA and miRNA therapeutics and a review of targeted nanoparticle delivery systems in breast cancer. Biophys Rev. 2018;10(1):69–86.
- Dana H, Chalbatani GM, Mahmoodzadeh H, et al. Molecular Mechanisms and Biological Functions of siRNA. Int J Biomed Sci. 2017;13(2):48–57.