scholarly journals The decisive role of the water structure in changes of conformation of nucleic acids.

1999 ◽  
Vol 46 (1) ◽  
pp. 133-144 ◽  
Author(s):  
J Barciszewski ◽  
J Jurczak ◽  
S Porowski ◽  
T Specht ◽  
V A Erdmann

This review summarizes data on the structure and properties of water under normal conditions, at high salt concentration and under high pressure. We correlate the observed conformational transitions in nucleic acids with changes in water structure and activity, and suggest a mechanism of conformational transitions of nucleic acid involving these changes. We conclude that the Z-DNA form is induced only at low water activity caused by high salt concentrations and/or high pressure.

2001 ◽  
Vol 260 (2) ◽  
pp. 293-307 ◽  
Author(s):  
Jan Barciszewski ◽  
Janusz Jurczak ◽  
Sylwester Porowski ◽  
Thomas Specht ◽  
Volker A. Erdmann

2020 ◽  
Author(s):  
Mei Dang ◽  
Yifan Li ◽  
Jianxing Song

AbstractTDP-43 and hnRNPA1 contain tandemly-tethered RRM domains, which not only functionally bind an array of nucleic acids, but also participate in aggregation/fibrillation, a pathological hallmark of various human diseases including ALS, FTD, AD and MSP. Here, by DSF, NMR and MD simulations we systematically characterized stability, ATP-binding and conformational dynamics of TDP-43 and hnRNPA1 RRM domains in both tethered and isolated forms. The results reveal three key findings: 1) very unexpectedly, upon tethering TDP-43 RRM domains become dramatically coupled and destabilized with Tm reduced to only 49 °C. 2) ATP specifically binds TDP-43 and hnRNPA1 RRM domains, in which ATP occupies the similar pockets within the conserved nucleic-acid-binding surfaces, with the affinity higher to the tethered than isolated forms. 3) MD simulations indicate that the tethered RRM domains of TDP-43 and hnRNPA1 have higher conformational dynamics than the isolated forms. Two RRM domains become coupled as shown by NMR characterization and analysis of inter-domain correlation motions. The study explains the long-standing puzzle that the tethered TDP-43 RRM1-RRM2 is particularly prone to aggregation/fibrillation, and underscores the general role of ATP in inhibiting aggregation/fibrillation of RRM-containing proteins. The results also rationalize the observation that the risk of aggregation-causing diseases increases with aging.


2020 ◽  
Vol 21 (6) ◽  
pp. 2001
Author(s):  
Silvia Mercurio ◽  
Silvia Cauteruccio ◽  
Raoul Manenti ◽  
Simona Candiani ◽  
Giorgio Scarì ◽  
...  

The microRNAs are small RNAs that regulate gene expression at the post-transcriptional level and can be involved in the onset of neurodegenerative diseases and cancer. They are emerging as possible targets for antisense-based therapy, even though the in vivo stability of miRNA analogues is still questioned. We tested the ability of peptide nucleic acids, a novel class of nucleic acid mimics, to downregulate miR-9 in vivo in an invertebrate model organism, the ascidian Ciona intestinalis, by microinjection of antisense molecules in the eggs. It is known that miR-9 is a well-conserved microRNA in bilaterians and we found that it is expressed in epidermal sensory neurons of the tail in the larva of C. intestinalis. Larvae developed from injected eggs showed a reduced differentiation of tail neurons, confirming the possibility to use peptide nucleic acid PNA to downregulate miRNA in a whole organism. By identifying putative targets of miR-9, we discuss the role of this miRNA in the development of the peripheral nervous system of ascidians.


Development ◽  
1957 ◽  
Vol 5 (2) ◽  
pp. 111-121
Author(s):  
J. O. Lavarack

On the possible role of nucleic acids in organizer activity Brachet's (1940) histochemical researches show that a basophil cytoplasmic material, which he identifies with ribose nucleic acid, is present generally in regions of active differentiation and that it accumulates at interfaces between inductors and the cells responsive to them. These conclusions are supported by Gallera & Oprecht (1948). Further, it is known that much of the ribose nucleic acid of cytoplasm is bound to the submicroscopic particulates and certain observations suggest that neural induction (Holtfreter, 1933; Brachet, 1950) and induction of the lens vesicle (McKeehan, 1951) depend at some stage on contact or the transfer of relatively large particles from one cell group to another. It may well be that any chemical mechanisms concerned are complex and include chains of reactions involving a number of substances. Among possible participants nucleic acids are of particular interest because of their metabolic relationships with proteins.


2007 ◽  
Vol 85 (4) ◽  
pp. 283-292 ◽  
Author(s):  
Jelena Božilović ◽  
Jan W Bats ◽  
Joachim W Engels

Chemically modified bases are frequently used to stabilize nucleic acids, to study the driving forces for nucleic acid structure formation, and to tune DNA and RNA hybridization conditions. Nucleoside analogues are chemical means to investigate hydrogen bonds, base stacking, and solvation as the three predominant forces that are responsible for the stability of nucleic acids. To obtain deeper insight into the contributions of these interactions to RNA stability, we decided to synthesize some novel nucleic acid analogues where the nucleobases are replaced by fluoroindoles. Fluorinated indoles can be compared with fluorinated benzimidazoles to determine the role of nitrogen in five-membered ring systems. The synthesis of fluoroindole ribonucleosides as well as the X-ray crystal structures of all synthesized fluoroindole ribonucleosides are reported here. These compounds could also be building blocks for a variety of biologically active RNA analogues.Key words: indoles, nucleosides, crystal structure, glycosilation, indole-synthesis.


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