Is There a Role for Immunoregulatory and Antiviral Oligonucleotides Acting in the Extracellular Space? A Review and Hypothesis DOI Open Access
Aleksandra Dondalska, Sandra Pålsson, Anna‐Lena Spetz

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(23), P. 14593 - 14593

Published: Nov. 23, 2022

Here, we link approved and emerging nucleic acid-based therapies with the expanding universe of small non-coding RNAs (sncRNAs) innate immune responses that sense oligonucleotides taken up into endosomes. The Toll-like receptors (TLRs) 3, 7, 8, 9 are located in endosomes can detect acids through endocytic routes. These key triggers defense against viruses and/or bacterial infections, yet they also constitute an Achilles heel towards discrimination between self- pathogenic acids. compartmentalization activity nucleases components avoiding autoimmune reactions acids, but still lack knowledge on plethora might be released extracellular space upon inflammation, other stress involving increased cell death. We review recent findings a set single-stranded (length 25–40 nucleotides (nt)) temporarily block ligands destined for expressing TLRs human monocyte-derived dendritic cells. discuss gaps highlight existence pool RNA approximate length 30–40 nt may have unappreciated regulatory functions physiology as gatekeepers endosomal uptake certain

Language: Английский

Nucleolin in the cell membrane promotes Ang II-mediated VSMC phenotypic switching by regulating the AT1R internalization function DOI Creative Commons
Fang Li,

Zhijie Shen,

Yinzhuang Zhang

et al.

Biology Direct, Journal Year: 2025, Volume and Issue: 20(1)

Published: Feb. 26, 2025

Nucleolin (NCL) plays an important regulatory role in angiotensin II (Ang II)-induced phenotypic switching of vascular smooth muscle cells (VSMCs). The aim this study was to discuss its potential mechanisms. We investigated if the pathways involving Ang type 1 receptor (AT1R) and PKC/MAPK are responsible for II's effects on VSMC switching. upregulated NCL expression activated signaling pathway induce In addition, promoted translocation from nucleus cell membrane. shown bind AT1R, whereas binding AT1R greatly attenuated after deletion GAR region. when peptide-N-glycosidase F (PNGase F) applied, N-glycosylation protein were inhibited. II-induced internalization, overexpression delayed internalization by inhibiting phosphorylation recruited Rab4 Rab11 promote recycling, knockdown showed opposite effect reversal use rasarfin reversed sh-NCL. vivo experiments, inhibited blood pressure rise vasculopathy. Our demonstrates that promotes II-mediated VSMCs regulating function.

Language: Английский

Citations

1
New nucleolin-containing cytoplasmic bodies in an archamoebian protist Pelomyxa belevskii (Amoebozoa, Archamoebae, Pelobiontida) DOI
D. S. Bogolyubov, Ludmila Chistyakova,

Alexandra O. Travina

et al.

PROTOPLASMA, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Language: Английский

Citations

1
Treatment of acute myeloid leukemia models by targeting a cell surface RNA-binding protein DOI Creative Commons
Benson M. George, Maria Eleftheriou, Eliza Yankova

et al.

Nature Biotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: April 23, 2025

Abstract Immunotherapies for acute myeloid leukemia (AML) and other cancers are limited by a lack of tumor-specific targets. Here we discover that RNA-binding proteins glycosylated RNAs (glycoRNAs) form precisely organized nanodomains on cancer cell surfaces. We characterize nucleophosmin (NPM1) as an abundant surface protein (csNPM1) variety tumor types. With focus AML, observe csNPM1 blasts leukemic stem cells but not normal hematopoietic cells. develop monoclonal antibody to target csNPM1, which exhibits robust anti-tumor activity in multiple syngeneic xenograft models including patient-derived xenografts, without observable toxicity. find is expressed mutation-agnostic manner primary AML may therefore offer general strategy detecting treating AML. Surface profiling vivo work also demonstrate solid tumors. Our data suggest its neighboring glycoRNA–cell (csRBP) clusters serve alternative antigen class therapeutic targeting or identification.

Language: Английский

Citations

1
Viral respiratory infections and air pollution: A review focused on research in Poland DOI

Barbara Poniedziałek,

Piotr Rzymski, Dorota Zarębska‐Michaluk

et al.

Chemosphere, Journal Year: 2024, Volume and Issue: 359, P. 142256 - 142256

Published: May 7, 2024

Language: Английский

Citations

5
G-Quadruplexes in Nuclear Biomolecular Condensates DOI Open Access
Iuliia Pavlova, Mikhail Iudin, A. V. Surdina

et al.

Genes, Journal Year: 2023, Volume and Issue: 14(5), P. 1076 - 1076

Published: May 13, 2023

G-quadruplexes (G4s) have long been implicated in the regulation of chromatin packaging and gene expression. These processes require or are accelerated by separation related proteins into liquid condensates on DNA/RNA matrices. While cytoplasmic G4s acknowledged scaffolds potentially pathogenic condensates, possible contribution to phase transitions nucleus has only recently come light. In this review, we summarize growing evidence for G4-dependent assembly biomolecular at telomeres transcription initiation sites, as well nucleoli, speckles, paraspeckles. The limitations underlying assays remaining open questions outlined. We also discuss molecular basis apparent permissive role vitro condensate based interactome data. To highlight prospects risks G4-targeting therapies with respect transitions, touch upon reported effects G4-stabilizing small molecules nuclear condensates.

Language: Английский

Citations

11
The chromatin-associated lncREST ensures effective replication stress response by promoting the assembly of fork signaling factors DOI Creative Commons
Luisa Statello, José Miguel Fernández-Justel,

Jovanna González

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 1, 2024

ABSTRACT Besides the well-characterized protein network involved in replication stress response, several regulatory RNAs have been shown to play a role this critical process. However, it has remained elusive whether they act locally at stressed forks. Here, by investigating localizing on chromatin upon induced hydroxyurea, we identified set of lncRNAs upregulated S-phase and controlled transcription factors. Among them, demonstrate that previously uncharacterized lncRNA lncREST (long non-coding RNA REplication STress) is transcriptionally p53 localizes LncREST -depleted cells experience sustained fork progression accumulate un-signaled DNA damage. Under stress, interacts with NCL assists engaging its interaction RPA. The loss associated reduced NCL-RPA decreased RPA chromatin, leading defective signaling accumulation mitotic defects, resulting apoptosis reduction tumorigenic potential cancer cells. These findings uncover function favoring recruitment proteins sites replication.

Language: Английский

Citations

4
Complement 1q/Tumor Necrosis Factor-Related Proteins (CTRPs): Structure, Receptors and Signaling DOI Creative Commons

Constanze Schanbacher,

Heike M. Hermanns, Kristina Lorenz

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(2), P. 559 - 559

Published: Feb. 14, 2023

Adiponectin and the other 15 members of complement 1q (C1q)/tumor necrosis factor (TNF)-related protein (CTRP) family are secreted proteins composed an N-terminal variable domain followed by a stalk region characteristic C-terminal trimerizing globular C1q (gC1q) originally identified in subunits C1q. We performed basic PubMed literature search for articles mentioning various CTRPs or their receptors abstract title. In this narrative review, we briefly summarize biology focus then on structure, major signaling pathways CTRPs. Analyses CTRP knockout mice transgenic gave overwhelming evidence relevance anti-inflammatory insulin-sensitizing effects autoimmune diseases, obesity, atherosclerosis cardiac dysfunction. form homo- heterotypic trimers oligomers which can have different activities. The some unknown redundantly targeted several way activate to trigger downstream is largely unknown. considered as promising therapeutic targets but translational usage still hampered limited knowledge redundancy signal transduction.

Language: Английский

Citations

9
Current research on viral proteins that interact with fibrillarin DOI Open Access

Stefano Decle-Carrasco,

Alma Laura Rodríguez-Piña,

Luis Carlos Rodríguez‐Zapata

et al.

Molecular Biology Reports, Journal Year: 2023, Volume and Issue: 50(5), P. 4631 - 4643

Published: March 16, 2023

Language: Английский

Citations

9
A Twist in Yeast: New Perspectives for Studying TDP-43 Proteinopahies in S. cerevisiae DOI Creative Commons
Roberto Stella, Alessandro Bertoli, Raffaele Lopreiato

et al.

Journal of Fungi, Journal Year: 2025, Volume and Issue: 11(3), P. 188 - 188

Published: Feb. 28, 2025

TAR DNA-binding protein 43 kDa (TDP-43) proteinopathies are a group of neurodegenerative diseases (NDs) characterized by the abnormal accumulation TDP-43 in neurons and glial cells. These associated with several NDs, including amyotrophic lateral sclerosis, frontotemporal lobar degeneration, some forms Alzheimer’s disease. Yeast models have proven valuable ND research due to their simplicity, genetic tractability, conservation many cellular processes shared higher eukaryotes. For decades, Saccharomyces cerevisiae has been used as model organism study behavior toxicity TDP-43, facilitating identification genes pathways that either exacerbate or mitigate its toxic effects. This review will discuss evidence showing yeast exhibit defects proteostasis, mitochondrial function, autophagy, RNA metabolism, which key features TDP-43-related NDs. Additionally, we explore how modulating proteins involved these reduce toxicity, aiding restoring normal function preventing pathological aggregation. findings highlight potential therapeutic targets for treatment diseases.

Language: Английский

Citations

0
Unmodified RNA sequences form unusual stable G-quadruplexes with potential anti-RSV and anti-angiogenesis applications DOI Creative Commons
Ruhui Tian, Yue Gao, Xiaohui Hu

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 21, 2025

DNA or RNA sequences with customizable designs form unique three-dimensional structures that bind to targets high precision and strength, making them promising tools for medical diagnosis therapy. However, their clinical use is limited by rapid clearance from blood safety concerns. This study introduces a novel RNA-based structure called G-quadruplex, which requires no chemical modifications. These G-quadruplexes remain highly stable in biological fluids, retaining over 90% of concentration after 96 h. Experiments confirm strong binding cell surface protein (nucleolin) without significant cellular uptake, resulting nearly zero harm cells. They effectively block respiratory syncytial virus infection, suppress the growth movement human vessel cells, prevent new formation chicken embryos, even specialized delivery systems. G-quadruplex demonstrate dual potential treating cancers viral infections, offering versatile safe strategy future therapies. Stable (90% serum h) nucleolin, showing anti-viral (respiratory virus) anti-angiogenic effects low toxicity, tumor

Language: Английский

Citations

0