RNAses

Philips C M, Mizutani Y and Hochstrasser R M 1995 Ultrafast thermally induced unfolding of RNase A Proc. Natl Acad. Sol. USA 92 7292-6... 

The phosphorodithioates DNA derivatives have been shown to bind specifically to complementary DNA or ENA sequences to form stable adducts. Because they are also highly resistant to degradation by cellular exonucleases, these derivatives can be useful both for appHcations in research and as therapeutic dmgs. Phosphorodithioate DNA has been shown to stimulate Rnase H activity in nuclear cell extracts and is a potent inhibitor of HIV type-1 reverse transcriptase (56). 

RNase Bovine ribonnclease A, an enzyme 124 amino acid residues. Note diat RNase lacks tryptophan. 

Fike most enzymes (see Chapter 14), nucleases exhibit selectivity or specificity for the nature of the substance on which they act. That is, some nucleases act only on DNA (DNases), while others are specific for RNA (the RNases). Still... 

RNase A (pancreas) RNA b Where 3 -P04 is to pyrimidine oligos with pyrimidine 3 -P04 ends... 

FIGURE 11.32 All example of nuclease specificity The specificity of RNA hydrolysis by bovine pancreatic RNase. This RNase cleaves h at 3 -pyriinidines, yielding oligonncleoddes with pyrimidine 3 -P04 ends. 

Add RNase H, DNA polymerase, and dATP, dTTP, dGTP, dCTP mRNA degraded by RNase T... 

ASON are sequences of usually 17-30 bases of single-stranded DNA that hybridize to specific genes or their mRNA products by Watson-Crick base pairing and disrupt their function. In the case of AS-ODN (antisense oligodeoxyribonucleotides) cellular RNAseH is able to bind to the DNA-RNA duplex and hydrolyze the RNA, resulting in increased transcript turnover. Modifications to the deoxy moiety at the 2 -sugar position prohibits RNAse H action. 

The short length of a typical ASON facilitates cell internalization and increases hybridization efficiency by reducing base-mismatch errors. Once hybridization has occurred the ASON-mRNA complex becomes a substrate for intracellular RNAses (e.g., RNAse-H) that catalyze mRNA degradation and allow ASON to recycle for another base pairing with the next target mRNA molecule. The net result of this process is a sustained decrease of target mRNA translation and a lower intracellular level of the corresponding protein (Fig. 1). 

The ribozymes were widely modified and can be further subdivided according to their structural features in group I ribozymes, hammerhaed ribozymes, hairpin ribozymes, ribonucelase P (RNase P), and hepatitis delta virus ribozymes. 

Dicer represents the key enzyme in the RNAi pathway. Dicer is also known as Helicase with RNAse motif, heRNA, Helicase-moi, K12H4.8-like, or KIAA0928. Dicer produces cleaves long double-stranded RNA into small pieces of about 21-23 nucleotides. These so-called siRNA duplexes produced by the action of Dicer contain 5 -phosphates and free 3 -hydroxylgroups... 

RNAse is an enzyme that catalyses the breakdown of RNA molecules into their component nucleotides. RNAses are extremely common in the modern world, resulting in very short life spans for any RNA that is not in a protected environment. 

Matzen K, Elzaouk L, Matskevich AA, Nitzsche A, Heinrich J, Moelling K (2007) RNase H-mediated retrovirus destruction in vivo triggered by oUgodeoxynucleotides.Nat Biotechnol 25 669-674... 

OAS 2 -5 oligoadenylate synthetase Activate a latent endoribonuclease, RNAse L, which degrades viral and cellular mRNAs and rRNAs... 

ISG20 IFN-stimulated gene product of 20kDA A member of the DEDD exonuclease superfamily with RNAse and DNAse activity... 

Li XL, Blackford JA, Hassel BA (1998b) RNase L mediates the antiviral effect of interferon through a selective reduction in viral RNA during encephalomyocarditis virus infection. J Virol 72 2752-2759... 

Brown P.H., Bruckenstein D.A., Han-VEY J.C., et al.An assessment of the anti-sense properties of RNase FI-competent and steric-blocking oligomers. Nucleic Acids Res. 1995 23 1197-1203. 

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... 

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