Phase Separation Modulates the Formation and Stabilities of DNA Guanine Quadruplex

Gao, Zi; Yuan, Jun; He, Xiaomei; Wang, Handing; Wang, Yinsheng

doi:10.1021/jacsau.3c00106

Cited by 3 publications

(1 citation statement)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Biomolecular condensates are microscale subcellular compartments that lack surrounding membranes but function to concentrate proteins and/or nucleic acids in eukaryotic cells. − These condensates play important roles in regulation of cellular processes, such as subcellular organization of biochemical reactions, gene regulation, and stress response. − Typically, the condensates comprise two types of components: the “scaffolds” that drive the condensate assembly and the biomolecular “clients” that selectively partition into the condensates to endow biological functions . Inspired by this organization principle of natural condensates, various scaffold molecules, such as intrinsically disordered proteins, folded-domain repeat proteins, or RNA, have been engineered to construct synthetic condensates with on-demand functions in eukaryotic cells .…”

Section: Introductionmentioning

confidence: 99%

Spatiotemporal Organization of Functional Cargoes by Light-Switchable Condensation in Escherichia coli Cells

Pan,

Zu,

Zhu

et al. 2024

JACS Au

View full text Add to dashboard Cite

Biomolecular condensates are dynamic subcellular compartments that lack surrounding membranes and can spatiotemporally organize the cellular biochemistry of eukaryotic cells. However, such dynamic organization has not been realized in prokaryotes that naturally lack organelles, and strategies are urgently needed for dynamic biomolecular compartmentalization. Here we develop a light-switchable condensate system for on-demand dynamic organization of functional cargoes in the model prokaryotic Escherichia coli cells. The condensate system consists of two modularly designed and genetically encoded fusions that contain a condensation-enabling scaffold and a functional cargo fused to the blue light-responsive heterodimerization pair, iLID and SspB, respectively. By appropriately controlling the biogenesis of the protein fusions, the condensate system allows rapid recruitment and release of cargo proteins within seconds in response to light, and this process is also reversible and repeatable. Finally, the system is demonstrated to dynamically control the subcellular localization of a cell division inhibitor, SulA, which enables the reversible regulation of cell morphologies. Therefore, this study provides a new strategy to dynamically control cellular processes by harnessing light-controlled condensates in prokaryotic cells.

show abstract

Section: Introductionmentioning

confidence: 99%

Spatiotemporal Organization of Functional Cargoes by Light-Switchable Condensation in Escherichia coli Cells

Pan,

Zu,

Zhu

et al. 2024

JACS Au

View full text Add to dashboard Cite

show abstract

Predicting nuclear G-quadruplex RNA-binding proteins with roles in transcription and phase separation

Luige,

Armaos,

Tartaglia

et al. 2024

Nat Commun

View full text Add to dashboard Cite

RNA-binding proteins are central for many biological processes and their characterization has demonstrated a broad range of functions as well as a wide spectrum of target structures. RNA G-quadruplexes are important regulatory elements occurring in both coding and non-coding transcripts, yet our knowledge of their structure-based interactions is at present limited. Here, using theoretical predictions and experimental approaches, we show that many chromatin-binding proteins bind to RNA G-quadruplexes, and we classify them based on their RNA G-quadruplex-binding potential. Combining experimental identification of nuclear RNA G-quadruplex-binding proteins with computational approaches, we build a prediction tool that assigns probability score for a nuclear protein to bind RNA G-quadruplexes. We show that predicted G-quadruplex RNA-binding proteins exhibit a high degree of protein disorder and hydrophilicity and suggest involvement in both transcription and phase-separation into membrane-less organelles. Finally, we present the G4-Folded/UNfolded Nuclear Interaction Explorer System (G4-FUNNIES) for estimating RNA G4-binding propensities at http://service.tartaglialab.com/new_submission/G4FUNNIES.

show abstract

Cell redistribution of G quadruplex‐structured DNA is associated with morphological changes of nuclei and nucleoli in neurons during tau pathology progression

Comptdaer,

Tardivel,

Schirmer

et al. 2024

Brain Pathology

View full text Add to dashboard Cite

While the double helical structure has long been its iconic representation, DNA is structurally dynamic and can adopt alternative secondary configurations. Specifically, guanine‐rich DNA sequences can fold in guanine quadruplexes (G4) structures. These G4 play pivotal roles as regulators of gene expression and genomic stability, and influence protein homeostasis. Despite their significance, the association of G4 with neurodegenerative diseases such as Alzheimer's disease (AD) has been underappreciated. Recent findings have identified DNA sequences predicted to form G4 in sarkosyl‐insoluble aggregates from AD brains, questioning the involvement of G4‐structured DNA (G4 DNA) in the pathology. Using immunofluorescence coupled to confocal microscopy analysis we investigated the impact of tau pathology, a hallmark of tauopathies including AD, on the distribution of G4 DNA in murine neurons and its relevance to AD brains. In healthy neurons, G4 DNA is detected in nuclei with a notable presence in nucleoli. However, in a transgenic mouse model of tau pathology (THY‐Tau22), early stages of the disease exhibit an impairment in the nuclear distribution of G4 DNA. In addition, G4 DNA accumulates in the cytoplasm of neurons exhibiting oligomerized tau and oxidative DNA damage. This altered distribution persists in the later stage of the pathology when larger tau aggregates are present. Still cytoplasmic deposition of G4 DNA does not appear to be a critical factor in the tau aggregation process. Similar patterns are observed in neurons from the AD cortex. Furthermore, the disturbance in G4 DNA distribution is associated with various changes in the size of neuronal nuclei and nucleoli, indicative of responses to stress and the activation of pro‐survival mechanisms. Our results shed light on a significant impact of tau pathology on the dynamics of G4 DNA and on nuclear and nucleolar mechanobiology in neurons. These findings reveal new dimensions in the etiopathogenesis of tauopathies.

show abstract

Phase Separation Modulates the Formation and Stabilities of DNA Guanine Quadruplex

Cited by 3 publications

References 53 publications

Spatiotemporal Organization of Functional Cargoes by Light-Switchable Condensation in Escherichia coli Cells

Spatiotemporal Organization of Functional Cargoes by Light-Switchable Condensation in Escherichia coli Cells

Predicting nuclear G-quadruplex RNA-binding proteins with roles in transcription and phase separation

Cell redistribution of G quadruplex‐structured DNA is associated with morphological changes of nuclei and nucleoli in neurons during tau pathology progression

Contact Info

Product

Resources

About