Structural analysis and cellular visualization of APP RNA G-quadruplex

Lyu, Kaixin; Chen, Shuo-Bin; Chan, Chun‐Yin; Tan, Jia‐Heng; Kwok, Chun Kit

doi:10.1039/c9sc02768h

Cited by 27 publications

(23 citation statements)

References 37 publications

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“…Finally, RNA G-quadruplex structure-selective binding of Nmethyl mesoporphyrin IX (NMM) was employed to confirm the G-quadruplex structures formation in 13385/PQS and 24268/PQS. NMM is a fluorescence light-up probe upon binding to the Gquadruplex structures [26,27]. The much stronger fluorescence in K + than Li + condition results from the specifically binding of NMM to RNA G-quadruplex, which suggests the formation of G-quadruplex structures in PQSs at positions of 13385 and 24268 ( Figure 2C and F).…”

Section: G-quadruplex Formation Confirmed By Multiple Spectroscopic Amentioning

confidence: 97%

Discovery of G-quadruplex-forming sequences in SARS-CoV-2

Juhas

Tsang

et al. 2020

Briefings in Bioinformatics

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117

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The outbreak caused by the novel coronavirus SARS-CoV-2 has been declared a global health emergency. G-quadruplex structures in genomes have long been considered essential for regulating a number of biological processes in a plethora of organisms. We have analyzed and identified 25 four contiguous GG runs (G2NxG2NyG2NzG2) in the SARS-CoV-2 RNA genome, suggesting putative G-quadruplex-forming sequences (PQSs). Detailed analysis of SARS-CoV-2 PQSs revealed their locations in the open reading frames of ORF1 ab, spike (S), ORF3a, membrane (M) and nucleocapsid (N) genes. Identical PQSs were also found in the other members of the Coronaviridae family. The top-ranked PQSs at positions 13385 and 24268 were confirmed to form RNA G-quadruplex structures in vitro by multiple spectroscopic assays. Furthermore, their direct interactions with viral helicase (nsp13) were determined by microscale thermophoresis. Molecular docking model suggests that nsp13 distorts the G-quadruplex structure by allowing the guanine bases to be flipped away from the guanine quartet planes. Targeting viral helicase and G-quadruplex structure represents an attractive approach for potentially inhibiting the SARS-CoV-2 virus.

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Section: G-quadruplex Formation Confirmed By Multiple Spectroscopic Amentioning

confidence: 97%

Discovery of G-quadruplex-forming sequences in SARS-CoV-2

Juhas

Tsang

et al. 2020

Briefings in Bioinformatics

Self Cite

117

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“…Their dysregulation due to mutations in the RG4-forming sequences or via the alteration of the association with trans factors contributes to human pathologies such as neurodegenerative diseases, cancer, or microbial infections ( Figure 1). The pervasive nature of RG4s has been demonstrated by surveying the extent of their structuration both in vitro using transcriptome-wide reverse transcriptase stalling assay [3,4] and in cellulo using imaging studies with antibodies [26] or molecular probes [27][28][29][30][31] (Box 1). By contrast, but consistent with previous in cellulo RNA folding studies [32], RG4s in mRNAs appeared to be predominantly unfolded in steady-state RG4-seq experiments in human cells [3].…”

Section: Rg4 Folding Dynamicsmentioning

confidence: 99%

G-Quadruplexes in RNA Biology: Recent Advances and Future Directions

Dumas

Herviou

Dassi

et al. 2021

Trends in Biochemical Sciences

135

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“…Folded rG4s tend to stall the reverse transcriptase, leading to rG4-specific truncations that can be detected by comparing the two resultant cDNA libraries. This method has detected many rG4s in the transcriptomes of human, plant and bacterial cells 18–20 , some of which have functional consequences in gene translation 19–22 . Here we performed rG4-seq on the highly A/U-biased transcriptome of P. falciparum and investigated the biological roles of rG4s in this parasite.…”

Section: Introductionmentioning

confidence: 99%

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

Dumetz

Chow

Harris

et al. 2021

Preprint

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G-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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Structural analysis and cellular visualization of APP RNA G-quadruplex

Abstract: This work introduces a multidisciplinary strategy to characterize the structure, folding status, and function of the RNA G-quadruplex in APP 3′UTR.

Cited by 27 publications

References 37 publications

Discovery of G-quadruplex-forming sequences in SARS-CoV-2

Discovery of G-quadruplex-forming sequences in SARS-CoV-2

G-Quadruplexes in RNA Biology: Recent Advances and Future Directions

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

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