Polyribonucleotide complexes

Crystals of Polyribonucleotide Complexes" in Liquid Crystals and Ordered Fluids, J.F. Johnson and R.S. Porter, Eds., Plenum Publ. Co., N.Y. (1978). 

Steinberg et al. (1969) have shown the existence of antibodies binding specifically with poly rl-poly rC labelled with in the sera of NZB and NZB/W mice as well as in the sera of SLE patients. This reaction can be inhibited by double-helical polyribonucleotide complexes. They showed also that these antibodies are different from anti-native DNA antibodies because the latter are not inhibited by double-helical polyribonucleotides. They later confirmed these results (Talal et al., 197I) by studies of reciprocal inhibition... 

When this synthetic polyribonucleotide complex, poly I poly C adsorbed onto methylated serum albumin is used as immunogen, antibodies reacting... 

Poly rG poly rC differs from the other polyribonucleotide complexes not only when it is tested as antigen but also when it is used as immunogen, as we shall describe later. 

Thus poly A poly U and poly I poly C induce antibodies specific for the double-stranded structure, and reciprocal cross-reactions between these two polyribonucleotide complexes are constant and quantitatively comparable. A third complex, poly G poly C reacts only feebly with the two preceding immune sera. The h3q)othesis that this immunochemical difference correlates with a stereochemical difference of structure implies that this complex, if it has immunogenic capacity, may induce antibodies with a particular specificity. The validity of this concept has been demonstrated and wiU be discussed next. 

Polyribonucleotides RNA-PolyP-Ca2+(Mg2+)-complexes PolyP-PHB-Ca2+ (ribozyme catalysis) (regulation of catalysis) (channels in lipid bilayers)... 

In the previous chapters the reactivity of metal ions with the monomer units of nucleic acids has been discussed. This section will deal with the binding of transition metals to the polynucleotides. There are also three types of complexes to be expected the metal-ring, the intermediate and the metal chain complex. The effect of the ribose or deoxyribose residue on the stability constants can be neglected since the reactivity of these sugars with cations is extremely low. However, as it will be seen later, the hydrolysis of polyribonucleotides is markedly facilitated by interaction of metal ions with the 2 —OH groups of the ribose. 

When RNA and other polyribonucleotides are heated with zinc ions a degradation of the polynucleotide chains occurs (12) within a 2 hrs period while DNA remains unaffected. This effect is similar to that obtained with La3+ (3, 23) and Cu2+ (12). According to this behavior it has to be emphasized that there must be a fourth type of metal nucleotide complex involving the 2 -0H group of the ribose moiety. It would be a valuable task to elucidate the precise structure of this type of complex... 

It is interesting that the surface denaturation of dh DNA is inhibited by the formation of covalent interstrand cross-links formed in DNA by bifunctional platinum coordination complexes - cis-diamminedichloro-platinum (II) and its trans-isomer [115]. The half-time of the interfacial denaturation of dh DNA in alkaline medium of ionic strength of 0.5 is c. 20 s [102] and is lowered with decreasing ionic strength [112]. The experiments carried out on dh DNAs of various base content indicate that the segments in dh DNA rich in adenine.thymine pairs are more susceptible to this kind of denaturation than those rich in guanine-cytokine pairs [115]. The surface denaturation at the mercury electrode has also been observed in dh RNA and dh complexes of synthetic polydeoxy- and polyribonucleotides [112, 116]. 

Table 3 (section 3.2.2.2) contains melting temperatures of polyribonucleotide hetero-complexes (including base-modified complexes), both double and triple stranded. 

Column 3 RNA species. RNAs and pol mucleotides arranged alphabetically under each metal oxidation state and metal complex first by polyribonucleotide species, then by tRNA species in order of amino acid and then source organism, mixed (unfractionated) species listed after those identified by amino acid, and finally by RNA species other than tRNAs. Amino acids are abbreviated by the three letter nomenclature, Ala , Arg , etc. Met P and Met m .represent the translational initiator and the ordinary methionine spedes, respectively. TYMV=turnip yellow mosaic virus. TMV=tobacco mosaic virus. 

Upon the formation of an open-promoter complex, polyribonucleotide chain formation may commence. RNA polymerase contains two nucleotide-binding sites called the initiation and the elon-... 

In order to give DNA immunizing properties Plescia et al. (1964, 1965) complexed the material to MBS A. A certain number of polynucleotides such as denatured DNA, poly dAT, and tRNA associated with MBS A have been used as immunogens by these authors. This method of preparation has been used for other polynucleotides, particularly for single-stranded synthetic polynucleotides and the various double- and triple-hehcal complexes formed from such polyribonucleotides. It appears that secondary structure of these complexes is generally maintained on adsorption onto MBS A, although some of their characteristics could well be modified in this electrostatic interaction. 

In order to elucidate the role of conformation of the immunogen, animals were immunized with complexes of polyribonucleotides (double- or triple-stranded) associated with MBS A. The antibodies obtained reacted specifically with double- or triple-stranded complexes and it was concluded that the specificity was determined by the macromolecular conformation of the immunogen (Nahon et al., 1967 Lacour et al., 1968 Michelson et al., 1971). Immunization of rabbits with DNA-MBSA or with double-stranded polynucleotide complexes adsorbed to MBS A ehcits antibodies belonging to the macroglobulin class (Stollar and Sandberg, 1966 Nahon-Merlin et al., 1973). 

Differences in the capacity of inhibition by polynucleotides not involved in complementary hydrogen bonds and by double-helical complexes of synthetic polyribonucleotides, or double-stranded viral RNA allow the conclusion that it is above all the regions of associated base pairs which are recognized in the RNA by anti-poly I poly C antibodies. Such complementary double-stranded helical regions have been described especially in tRNA but they have also been shown to exist in ribosomal RNA. These two kinds of RNA were therefore isolated and studied separately. Although both fractions precipitate anti-poly I poly C antibodies, their reactivity is nevertheless very different and rRNA precipitates eight times as much antibody as tRNA. Since tRNA possesses an important tertiary structure, this low reactivity could be explained by the non-accessibility of antigenic sites. 

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