Small interfering RNAs strand

Small interfering RNAs (siRNA) are the mediators of gene-specific silencing by RNA interference. SiRNA stands for small interfering RNA duplexes. They are typically 21-23 bp in length. SiRNA were either chemically synthesised for experimental purposes or produced by Dicer-mediated cleavage of long double-stranded RNA. 

Recently, the related phenomenon of RNA interference (RNAi) has attracted much attention [5]. RNAi occurs when a short (generally 21 nucleotides in length) double-stranded RNA (dsRNA) catalyticaUy represses the translation of a fully complementary mRNA sequence. The process appears to proceed via a complex formed between the antisense RNA strand and a protein with RNase activity [6]. Upon binding to the target mRNA sequence, the ribonucleoprotein complex initiates cleavage of the mRNA transcript thus preventing translation of intact protein. After dissociation from the truncated mRNAs, the ribonucleoprotein complex is free to act on other intact mRNAs. Such small interfering RNAs (siRNAs) have... 

RNA interference (RNAi) is a cellular defense mechanism through which double stranded RNAs (dsRNAs) are processed into short lengths of small interfering RNAs (siRNAs) of 20-25 nucleotides by an enzyme called Dicer (Fig. 3.10). 

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

Fig. 22.1. A model of gene silencing. Long, double-stranded RNAs (dsRNAs) are processed into 20-26 nucleotide small interfering RNAs (siRNAs) by Dicer (Step 1). The siRNAs associate with an RNA-induced silencing complex (RISC, Step 2), unwinding and activating in the process (Step 3). The antisense strand of the siRNA guides the RISC to complementary mRNA molecules (Step 4), which are cleaved and destroyed (Step 5). Sense and antisense RNA strands are indicated by thick and thin lines, respectively.

Fig. 2 The RNAi mechanisms. In the cytoplasm, dsRNA is cleaved into 22nt fragments called small interfering RNAs (siRNAs) by the RNase III t5rpe enzyme Dicer. The siRNAs are unwound and serve either as primers for RdRP (left) in some taxa (e.g., plants and nematodes) or, more universally, as guide strand in the RISC (right). RdRP creates additional dsRNA, amplifying the substrate for Dicer. RISC cleaves the target RNA in the region bound by the siRNA guide.

Sioud M. Single-stranded small interfering RNA are more immunostimulatory than their double-stranded counterparts a central role for 2 -hydroxyl uridines in immune responses. Eur ]Immunol. 2006 36 1222-1230. 

RNAi, first described in plants and termed cosuppression (reviewed in [21]), is a process in which double-stranded RNA induces homology-dependent degradation of mRNA [22-24]. RNAi is a process involving small interfering double-stranded... 

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. 

RNA interference. An enzyme complex called Dicer cleaves double-stranded RNA into small interfering RNAs (siRNA). These then bind to a protein complex called RNA-induced silencing complex (RISC). RISC unwinds the siRNA and one strand binds to the complementary mRNA, which is subsequently degraded. 

Figure 5.7 The mechanism of RNAi. (a) Long dsRNA is cleaved by the ribonuclease Dicer to form double stranded 21-25 nucleotide fragments called siRNAs. (b) siRNAs can also be introduced directly into the cells. In either case, association of the antisense strand with the RISC guides the resulting complex to its cognate mRNA site, where the mRNA is cleaved, selectively blocking protein translation. (Reprinted with permission from Manoharan, M. RNA interference and chemically modified small interfering RNAs. Curr. Opin. Chem. Biol. 2004, 8, 570-579, copyright 2004, Elsevier.)...

Figure 13.14 Schematic representation of RNA Interference. Small interfering RNA (siRNA) is generated by Dicer (RNase) cleavage of a short hairpin RNA (shRNA) into small double-stranded RNA (dsRNA) of 21-25 nucleotide lengths, or transfected into the cell. The transfected siRNA is phosphorylated at 5 -ends by an endogenous kinase. The 5 -phosphorylated siRNA is incorporated into RNA-induced silencing complex (RISC) and unfolded. The antisense strand targets the RISC to homologous mRNA (sequence complementary to the siRNA guide) which is then cleaved by an endonuclease in the RISC complex (termed Sheer). The mRNA initially cleaved by Sheer is degraded by exonucleases and thus silenced...

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]. 

---