scholarly journals Properties and biological impact of RNA G-quadruplexes: from order to turmoil and back

2020 ◽  
Vol 48 (22) ◽  
pp. 12534-12555
Author(s):  
Prakash Kharel ◽  
Gertraud Becker ◽  
Vladimir Tsvetkov ◽  
Pavel Ivanov
Keyword(s):  
Biological Significance ◽  
Underlying Disease ◽  
Chemical Imaging ◽  
Live Cells ◽  
Health And Disease ◽  
Vitro Analysis ◽  
In Vitro Analysis ◽  
Dynamic Fluctuation

Abstract Guanine-quadruplexes (G4s) are non-canonical four-stranded structures that can be formed in guanine (G) rich nucleic acid sequences. A great number of G-rich sequences capable of forming G4 structures have been described based on in vitro analysis, and evidence supporting their formation in live cells continues to accumulate. While formation of DNA G4s (dG4s) within chromatin in vivo has been supported by different chemical, imaging and genomic approaches, formation of RNA G4s (rG4s) in vivo remains a matter of discussion. Recent data support the dynamic nature of G4 formation in the transcriptome. Such dynamic fluctuation of rG4 folding-unfolding underpins the biological significance of these structures in the regulation of RNA metabolism. Moreover, rG4-mediated functions may ultimately be connected to mechanisms underlying disease pathologies and, potentially, provide novel options for therapeutics. In this framework, we will review the landscape of rG4s within the transcriptome, focus on their potential impact on biological processes, and consider an emerging connection of these functions in human health and disease.

scholarly journals In vitro analysis of elongation and termination by mutant RNA polymerases with altered termination behavior.

1996 ◽  
Vol 16 (11) ◽  
pp. 6468-6476 ◽  
Author(s):  
S A Shaaban ◽  
E V Bobkova ◽  
D M Chudzik ◽  
B D Hall
Keyword(s):  
Rna Polymerase Iii ◽  
Multiple Roles ◽  
Wild Type ◽  
Protein Motifs ◽  
Study Support ◽  
Vitro Analysis ◽  
Pol Iii ◽  
In Vitro Analysis

We have studied the in vitro elongation and termination properties of several yeast RNA polymerase III (pol III) mutant enzymes that have altered in vivo termination behavior (S. A. Shaaban, B. M. Krupp, and B. D. Hall, Mol. Cell. Biol. 15:1467-1478, 1995). The pattern of completed-transcript release was also characterized for three of the mutant enzymes. The mutations studied occupy amino acid regions 300 to 325, 455 to 521, and 1061 to 1082 of the RET1 protein (P. James, S. Whelen, and B. D. Hall, J. Biol. Chem. 266:5616-5624, 1991), the second largest subunit of yeast RNA pol III. In general, mutant enzymes which have increased termination require a longer time to traverse a template gene than does wild-type pol III; the converse holds true for most decreased-termination mutants. One increased-termination mutant (K310T I324K) was faster and two reduced termination mutants (K512N and T455I E478K) were slower than the wild-type enzyme. In most cases, these changes in overall elongation kinetics can be accounted for by a correspondingly longer or shorter dwell time at pause sites within the SUP4 tRNA(Tyr) gene. Of the three mutants analyzed for RNA release, one (T455I) was similar to the wild type while the two others (T455I E478K and E478K) bound the completed SUP4 pre-tRNA more avidly. The results of this study support the view that termination is a multistep pathway in which several different regions of the RET1 protein are actively involved. Region 300 to 325 likely affects a step involved in RNA release, while the Rif homology region, amino acids 455 to 521, interacts with the nascent RNA 3' end. The dual effects of several mutations on both elongation kinetics and RNA release suggest that the protein motifs affected by them have multiple roles in the steps leading to transcription termination.

Multifactorial Regulation of Cardiac Gene Expression: an In Vivo and In Vitro Analysis

1995 ◽  
Vol 752 (1 Cardiac Growt) ◽  
pp. 370-386 ◽  
Author(s):  
J. L. SAMUEL ◽  
I. DUBUS ◽  
F. FARHADIAN ◽  
F. MAROTTE ◽  
P. OLIVIERO ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiac Gene Expression ◽  
Cardiac Gene ◽  
Vitro Analysis ◽  
In Vitro Analysis

scholarly journals Comprehensive In Vitro Analysis of Voriconazole Inhibition of Eight Cytochrome P450 (CYP) Enzymes: Major Effect on CYPs 2B6, 2C9, 2C19, and 3A

2008 ◽  
Vol 53 (2) ◽  
pp. 541-551 ◽  
Author(s):  
Seongwook Jeong ◽  
Phuong D. Nguyen ◽  
Zeruesenay Desta
Keyword(s):  
Cytochrome P450 ◽  
Liver Microsomes ◽  
Competitive Inhibitor ◽  
Major Effect ◽  
Cyp Enzymes ◽  
Human Cytochrome ◽  
Vitro Analysis ◽  
In Vitro Analysis

ABSTRACT Voriconazole is an effective antifungal drug, but adverse drug-drug interactions associated with its use are of major clinical concern. To identify the mechanisms of these interactions, we tested the inhibitory potency of voriconazole with eight human cytochrome P450 (CYP) enzymes. Isoform-specific probes were incubated with human liver microsomes (HLMs) (or expressed CYPs) and cofactors in the absence and the presence of voriconazole. Preincubation experiments were performed to test mechanism-based inactivation. In pilot experiments, voriconazole showed inhibition of CYP2B6, CYP2C9, CYP2C19, and CYP3A (half-maximal [50%] inhibitory concentrations, <6 μM); its effect on CYP1A2, CYP2A6, CYP2C8, and CYP2D6 was marginal (<25% inhibition at 100 μM voriconazole). Further detailed experiments with HLMs showed that voriconazole is a potent competitive inhibitor of CYP2B6 (Ki < 0.5), CYP2C9 (Ki = 2.79 μM), and CYP2C19 (Ki = 5.1 μM). The inhibition of CYP3A by voriconazole was explained by noncompetitive (Ki = 2.97 μM) and competitive (Ki = 0.66 μM) modes of inhibition. Prediction of the in vivo interaction of voriconazole from these in vitro data suggests that voriconazole would substantially increase the exposure of drugs metabolized by CYP2B6, CYP2C9, CYP2C19, and CYP3A. Clinicians should be aware of these interactions and monitor patients for adverse effects or failure of therapy.

Predicting gallstone composition with CT: in vivo and in vitro analysis.

Radiology ◽  
1990 ◽  
Vol 174 (2) ◽  
pp. 337-341 ◽  
Author(s):  
K Brakel ◽  
J S Laméris ◽  
H G Nijs ◽  
O T Terpstra ◽  
G Steen ◽  
...  
Keyword(s):  
Vitro Analysis ◽  
Gallstone Composition ◽  
In Vitro Analysis

scholarly journals In Vivo and In Vitro Analysis of Rat Lumbar Spine Mechanics

2010 ◽  
Vol 468 (10) ◽  
pp. 2695-2703 ◽  
Author(s):  
Matthew E. Cunningham ◽  
Jocelyn M. Beach ◽  
Serkan Bilgic ◽  
Oheneba Boachie-Adjei ◽  
Marjolein C. H. van der Meulen ◽  
...  
Keyword(s):  
Lumbar Spine ◽  
Spine Mechanics ◽  
Vitro Analysis ◽  
In Vitro Analysis

scholarly journals Aggravated Lyme Carditis in CD11a−/− and CD11c−/− Mice

2005 ◽  
Vol 73 (11) ◽  
pp. 7637-7643 ◽  
Author(s):  
Mireia Guerau-de-Arellano ◽  
Joseph Alroy ◽  
Daniel Bullard ◽  
Brigitte T. Huber
Keyword(s):  
Wild Type ◽  
Lyme Carditis ◽  
Disease Induction ◽  
In Vivo Analysis ◽  
The Common ◽  
Vitro Analysis ◽  
Β2 Integrins ◽  
In Vitro Analysis

ABSTRACT CD18 hypomorph mice expressing reduced levels of the common β2 integrin chain develop aggravated Lyme carditis, compared to that developed by wild-type (WT) mice, upon infection with the spirochete Borrelia burgdorferi. The enhancement of Lyme carditis in these mice is characterized by increased macrophage infiltration, correlating with augmented expression of the monocyte/macrophage chemoattractant protein 1 (MCP-1). The lack of CD18 results in the deficiency of all β2 integrins, i.e., CD11a/CD18 (LFA-1), CD11b/CD18 (Mac-1/CR3), CD11c/CD18 (p150,95/CR4), and CD11d/CD18. To determine the roles of the various β2 integrins in controlling the development of aggravated Lyme carditis, disease induction was analyzed in CD11a−/−, CD11b−/−, and CD11c−/− mice. CD11a−/− and CD11c−/− mice, but not CD11b−/− mice, developed aggravated Lyme carditis after exposure to B. burgdorferi. Similarly to CD18 hypomorph mice, CD11c−/− mice expressed higher levels of MCP-1, compared to both WT and CD11a−/− mice, as determined by in vitro analysis of MCP-1 secretion by bone marrow-derived dendritic cells and in vivo analysis of MCP-1 mRNA expression in B. burgdorferi-infected hearts. On the other hand, CD11a deficiency was associated with heightened heart B. burgdorferi burden relative to that of WT mice. Overall, our results suggest that the increased severity of Lyme carditis in CD18 hypomorph mice is caused by deficiency in CD11a or CD11c, possibly via different mechanisms.

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