Double-stranded RNA molecules

Genome The total genetic information present in an organism. Viral genomes are unusual in that they can be diverse. Examples of viral genomes include single-stranded DNA, single- and double-stranded RNA molecules. 

The phenomenon of RNA Interference, RNAI, Involves double-stranded RNA molecules... 

Small interfering RNA (siRNA)—Short double-stranded RNA molecules able... 

At the far left, we can see the nucleic acid and protein structures shown in frame 1. In addition, we show a much larger protein, the immunoglobulin G antibody molecule. Four separate polypeptide chains join to make up an antibody molecule two heavy chains (blue) of about 400 amino acids and two light chains (purple) of about 200 amino acids. The antibody is about 16 nm in width. Finally, at the far right, we show the core particle from a small plant virus, the reovirus. Only the icosahedral protein coat of the virus can be seen. The reovirus particle is about 60 nm across. The nucleic acids of the virus are sequestered inside the virus core. The reovirus family is unusual in that its nucleic acids are all double-stranded RNA molecules. 

Short interfering RNA (siRNA) is a class of molecules composed of double-stranded RNA molecules (20-25 nucleotides) that are involved with the interference of specific genes (i.e., RNA interference or RNAi). During the RNAi process, the siRNA is incorporated into a protein complex, which unwinds the siRNA by an ATP-dependent mechanism to generate an... 

An extremely powerful tool for disrupting gene expression was serendipi-tously discovered in the course of studies that required the introduction of RNA into a cell. The introduction of a specific double-stranded RNA molecule into a cell was found to suppress the transcription of genes that contained sequences present in the double-stranded RNA molecule. Thus, the introduction of a specific RNA molecule can interfere with the expression of a specific gene. 

Figure 5.36 RiNA interference mechanism. A double-stranded RNA molecule is cleaved into 21-bp fragments by the enzyme Dicer to produce siRNAs. These siRNAs are incorporated into the RNA-induced silencing complex (RISC), where the single-stranded RNAs guide the cleavage of mRNAs that contain complementary sequences.

Double-Stranded RNA Molecules Can Interfere with Gene Function by Targeting mRNA for Destruction... 

RNA Interference (RNAl) Is a process of post-transcriptlonal gene silencing mediated by short double-stranded RNA molecules called siRNA (small Interfering RNAs). In mammalian cells, transfection of 21-22 nucleotide siRNAs leads to degradation of mRNA molecules that contain the same sequence as the siRNA. In the following experiment, siRNA and knockout mice are used to Investigate two related cell surface proteins designated p24 and p25 that are suspected to be cellular receptors for the uptake of a newly Isolated virus. 

Double-stranded RNA molecules, although only discussed in a limited fashion, hold the best traits of DNA and proteins, i.e., siRNA s structure does not lend itself to high surface activity, and thus degradation by absorption to solid- or gas-liquid interfaces is not an issue. Furthermore, siRNA s small size is well below the continuum limit, and therefore, the molecule is not susceptible to shear-induced degradation. 

Fig. 8.2. Mechanism of action of siRNAs. The siRNAs are generated either from long, double-stranded RNA molecules processed by an enzyme called Dicer or by transfecting chemically synthesized double-stranded siRNA molecules into the cells. The siRNA is then incorporated into RNA-induced...

Finally, the newest molecules to induce excitement are the double-stranded sIRNAs. The RNA interference is initiated by long, double-stranded RNA molecules that are processed into 21- to 23-nucleotide RNAs. These sIRNAs are then incorporated into the RISC and serve to guide the nuclease that destroys the target RNA and stops protein synthesis. These molecules are extremely stable in the cell. In some experiments, they... 

The two species are quite similar the variations come from their source. MicroRNA comes from short endogenous hairpin loop structures, while siRNA molecules are produced from long double-stranded RNA molecules or giant hairpin molecules. The mature miRNA molecules are 22 nucleotide duplexes and usually repress translation of target mRNA sequences. The siRNAs are part of the antiviral defense system of the cell. 

Cohen and co-workers combined the unique characteristics of acetyl-dextran (Ac-DEX) and spermine with small interfering RNA - a class of double-stranded RNA molecules, 20-25 base pairs in length - as a delivery system. Ac-DEX possesses several characteristics suitable for the delivery of bioactive agents such as proteins. The novel system combined ease of synthesis and biocompatibility with the advantage of controlled release, i.e., sensitivity to physiologically relevant acidic conditions. Acid-catalysed hydrolysis of spermine-Ac-DEX generated spermine-modified dextran, which could be further metabolised in vivo by enzymes [13]. 

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