Conformational Dynamics of the RNA G-Quadruplex and its Effect on Translation Efficiency

During translation, intracellular mRNA folds co-transcriptionally and must refold following the passage of ribosome. The mRNAs can be entrapped in metastable structures during these folding events. In the present study, we evaluated the conformational dynamics of the kinetically favored, metastable, and hairpin-like structure, which disturbs the thermodynamically favored G-quadruplex structure, and its effect on co-transcriptional translation in prokaryotic cells. We found that nascent mRNA forms a metastable hairpin-like structure during co-transcriptional folding instead of the G-quadruplex structure. When the translation progressed co-transcriptionally before the metastable hairpin-like structure transition to the G-quadruplex, function of the G-quadruplex as a roadblock of the ribosome was sequestered. This suggested that kinetically formed RNA structures had a dominant effect on gene expression in prokaryotes. The results of this study indicate that it is critical to consider the conformational dynamics of RNA-folding to understand the contributions of the mRNA structures in controlling gene expression.

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Quaternary Ammonium Zinc Phthalocyanine: Inhibiting Telomerase by Stabilizing G quadruplexes and Inducing G-Quadruplex Structure Transition and Formation

ChemBioChem ◽

10.1002/cbic.200600554 ◽

2007 ◽

Vol 8 (7) ◽

pp. 775-780 ◽

Cited By ~ 58

Author(s):

Lige Ren ◽

Anming Zhang ◽

Jing Huang ◽

Ping Wang ◽

Xiaocheng Weng ◽

...

Keyword(s):

Quaternary Ammonium ◽

Zinc Phthalocyanine ◽

Structure Transition ◽

Quadruplex Structure ◽

G Quadruplex

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A novel G-quadruplex motif in the Human MET promoter region

Bioscience Reports ◽

10.1042/bsr20171128 ◽

2017 ◽

Vol 37 (6) ◽

Cited By ~ 2

Author(s):

Jing Yan ◽

Deming Zhao ◽

Liping Dong ◽

Shuang Pan ◽

Fengjin Hao ◽

...

Keyword(s):

Gene Expression ◽

Gene Expression Regulation ◽

Luciferase Assay ◽

Klenow Fragment ◽

Regulate Gene Expression ◽

Physiological Conditions ◽

Quadruplex Structure ◽

G Quadruplex ◽

Quadruplex Formation

It is known that the guanine-rich strands in proto-oncogene promoters can fold into G-quadruplex structures to regulate gene expression. An intramolecular parallel G-quadruplex has been identified in MET promoter. It acts as a repressor in regulating MET expression. However, the full guanine-rich region in MET promoter forms a hybrid parallel/antiparallel G-quadruplex structure under physiological conditions, which means there are some antiparallel and hybrid parallel/antiparallel G-quadruplex structures in this region. In the present study, our data indicate that g3-5 truncation adopts an intramolecular hybrid parallel/antiparallel G-quadruplex under physiological conditions in vitro. The g3-5 G-quadruplex structure significantly stops polymerization by Klenow fragment in K+ buffer. Furthermore, the results of circular dichroism (CD) spectra and polymerase stop assay directly demonstrate that the G-quadruplex structure in g3-5 fragment can be stabilized by the G-quadruplex ligand TMPyP4 (5,10,15,20-tetra-(N-methyl-4-pyridyl) porphine). But the dual luciferase assay indicates TMPyP4 has no effect on the formation of g3-5 G-quadruplex in HepG2 cells. The findings in the present study will enrich our understanding of the G-quadruplex formation in proto-oncogene promoters and the mechanisms of gene expression regulation.

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Hypothesis: Regulation of neuroplasticity may involve I-motif and G-quadruplex DNA formation modulated by epigenetic mechanisms

10.31234/osf.io/7uvhn ◽

2018 ◽

Author(s):

German I. Todorov ◽

Catarina Cunha

Keyword(s):

Gene Expression ◽

Synaptic Plasticity ◽

Epigenetic Mechanisms ◽

Rna Structures ◽

Regulatory Activity ◽

Dna Structures ◽

Dna And Rna ◽

Neuronal Mechanisms ◽

G Quadruplex

Recent studies demonstrated the existence in vivo of various functional DNA structures that differ from the double helix. The G-quadruplex (G4) and intercalated motif (I-motif or IM) DNA structures are formed as knots where, correspondingly, guanines or cytosines on the same strand of DNA bind to each other. There are grounds to believe that G4 and IM sequences play a significant role in regulating gene expression considering their tendency to be found in or near regulatory sites (such as promoters, enhancers, and telomeres) as well as the correlation between the prevalence of G4 or IM conformations and specific phases of cell cycle. Notably, G4 and IM capable sequences tend to be found on the opposite strands of the same DNA site with at most one of the two structures formed at any given time. The recent evidence that K+, Mg2+ concentrations directly affect IM formation (and likely G4 formation indirectly) lead us to believe that these structures may play a major role in synaptic plasticity of neurons, and, therefore, in a variety of central nervous system (CNS) functions including memory, learning, habitual behaviors, pain perception and others. Furthermore, epigenetic mechanisms, which have an important role in synaptic plasticity and memory formation, were also shown to influence formation and stability of G4s and IMs. Our hypothesis is that non-canonical DNA and RNA structures could be an integral part of neuroplasticity control via gene expression regulation at the level of transcription, translation and splicing. We propose that the regulatory activity of DNA IM and G4 structures is modulated by DNA methylation/demethylation of the IM and/or G4 sequences, which facilitates the switch between canonical and non-canonical conformation. Other neuronal mechanisms interacting with the formation and regulatory activity of non-canonical DNA and RNA structures, particularly G4, IM and triplexes, may involve microRNAs as well as ion and proton fluxes. We are proposing experiments in acute brain slices and in vivo to test our hypothesis. The proposed studies would provide new insights into fundamental neuronal mechanisms in health and disease and potentially open new avenues for treating mental health disorders.

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G-quadruplex RNA motifs influence gene expression in the malaria parasite Plasmodium falciparum

10.1101/2021.03.08.434398 ◽

2021 ◽

Author(s):

Franck Dumetz ◽

Eugene Yui-Ching Chow ◽

Lynne M. Harris ◽

Mubarak I. Umar ◽

Anders Jensen ◽

...

Keyword(s):

Gene Expression ◽

Plasmodium Falciparum ◽

Malaria Parasite ◽

Regulation Of Gene Expression ◽

Low Complexity ◽

Telomere Maintenance ◽

Translation Efficiency ◽

G Quadruplex

ABSTRACTG-quadruplexes are non-helical secondary structures that can fold in vivo in both DNA and RNA. In human cells, they can influence replication, transcription and telomere maintenance in DNA, or translation, transcript processing and stability of RNA. We have previously showed that G-quadruplexes are detectable in the DNA of the malaria parasite Plasmodium falciparum, despite a very highly A/T-biased genome with unusually few guanine-rich sequences. Here, we show that RNA G-quadruplexes can also form in P. falciparum RNA, using rG4-seq for transcriptome-wide structure-specific RNA probing. Many of the motifs, detected here via the rG4seeker pipeline, have non-canonical forms and would not be predicted by standard in silico algorithms. However, in vitro biophysical assays verified the formation of non-canonical motifs. The G-quadruplexes in the P. falciparum transcriptome are frequently clustered in certain genes and associated with regions encoding low-complexity peptide repeats. They are overrepresented in particular classes of genes, notably those that encode PfEMP1 virulence factors, stress response genes and DNA binding proteins. In vitro translation experiments and in vivo measures of translation efficiency showed that G-quadruplexes can influence the translation of P. falciparum mRNAs. Thus, the G-quadruplex is a novel player in post-transcriptional regulation of gene expression in this major human pathogen.

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