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RNA interference (RNAi)

Views: 0     Author: Site Editor     Publish Time: 2021-09-29      Origin: Wikipedia; Umass Chan Medial School


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RNA interference (RNAi)

RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by other names, including co-suppression, post-transcriptional gene silencing (PTGS), and quelling. The detailed study of each of these seemingly different processes elucidated that the identity of these phenomena were all actually RNAi.  Since the discovery of RNAi and its regulatory potentials, it has become evident that RNAi has immense potential in suppression of desired genes. RNAi is now known as precise, efficient, stable and better than antisense therapy for gene suppression. Antisense RNA produced intracellularly by an expression vector may be developed and find utility as novel therapeutic agents.During RNAi, long dsRNA is cut or "diced" into small fragments ~21 nucleotides long by an enzyme called "Dicer". These small fragments, referred to as small interfering RNAs (siRNA), bind to proteins from a special family: the Argonaute proteins. After binding to an Argonaute protein, one strand of the dsRNA is removed, leaving the remaining strand available to bind to messenger RNA target sequences according to the rules of base pairing: A binds U, G binds C, and vice versa. Once bound, the Argonaute protein can either cleave the messenger RNA, destroying it, or recruit accessory factors to regulate the target sequence in other ways.


RNAi is widely used by researchers to silence genes in order to learn something about their function. siRNAs can be designed to match any gene, can be manufactured cheaply, and can be readily administered to cells. One can now order commercially synthesized siRNAs to silence virtually any gene in a human or other organism's cell, dramatically accelerating the pace of biomedical research. Furthermore, the ability to turn off expression of a single gene makes RNAi an appealing therapeutic approach to treat infectious diseases or genetic disorders, such as those that result from the inappropriate and undesirable activity of a gene, as in many cancers and neurodegenerative diseases. There are currently several clinical trials testing the safety and effectiveness of siRNA drugs.


RNAi is much more than a research tool. RNAi encompasses an array of ancient and sophisticated cellular mechanisms that regulate a variety of biological functions. Argonaute proteins bind many naturally occurring small RNAs to defend against transposable elements, maintain chromosome structure and stability, and regulate developmental timing and differentiation. For example, microRNAs represent a natural form of developmentally-important siRNAs. Like siRNAs, microRNAs are made by Dicer, but microRNA derive from single-stranded RNAs that fold back on themselves to generate small regions of double-stranded RNA—so called "stem-loops"— instead of the long double-stranded RNA that produces siRNAs. microRNAs can guide Argonaute proteins to repress messenger RNAs that match the miRNA incompletely, allowing one microRNA to regulate hundreds of genes. Humans make more than 500 distinct microRNAs, and the inappropriate production of specific microRNAs has been linked to several diseases. Drugs to inhibit disease-causing microRNAs are now being tested as therapies for several human diseases.


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