G-quadruplex DNA and RNA in cellular senescence DOI Creative Commons

Rocio Diaz Escarcega,

Paul R. Marshall, Andrey S. Tsvetkov

et al.

Frontiers in Aging, Journal Year: 2024, Volume and Issue: 5

Published: Oct. 9, 2024

Normal cells divide, are damaged, and repaired across their lifetime. As age, they enter cellular senescence, characterized by a permanent state of cell-cycle arrest triggered various stressors. The molecular mechanisms that regulate senescent phenotypes have been actively investigated over the last several decades; however, one area has neglected is how G-quadruplex (G4) DNA RNA (G4-DNA G4-RNA) mediate senescence. These non-canonical four-stranded structures most normative RNA-dependent processes, such as transcription, replication, translation, well pathogenic mechanisms, including genomic instability abnormal stress granule function. This review also highlights contribution G4s to sex differences in age-associated diseases emphasizes potential translational approaches target senescence anti-aging through G4 manipulation.

Language: Английский

Emerging of Ultrafine Membraneless Organelles as the Missing Piece of Nanostress: Mechanism of Biogenesis and Implications at Multilevels DOI
Jia Liu,

Liuting Zheng,

Xinyue Li

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Understanding the interaction between nanomaterials and cellular structures is crucial for nanoparticle applications in biomedicine. We have identified a subtype of stress granules, called nanomaterial-provoked granules (NSGs), induced by gold nanorods (AuNRs). These NSGs differ from traditional SGs their physical properties biological functions. Uptake AuNRs causes reactive oxygen species accumulation protein misfolding cell, leading to NSG formation. Physically, gel-like core liquid-like shell, influenced positively HSP70 negatively HSP90 ubiquitin-proteasome system. promote assembly interacting with G3BP1, reducing energy needed liquid-liquid phase separation (LLPS). impact functions affecting mRNA surveillance activating Adenosine 5'-monophosphate (AMP)-activated kinase signaling, response. Our study highlights role LLPS nanomaterial metabolism suggests as potential targets drug delivery strategies, advancing field nanomedicine.

Language: Английский

Citations

0
KPNA2 promotes osteosarcoma progression by regulating the alternative splicing of DDX3X mediated by YBX1 DOI Creative Commons
Li Cao, Ke Jia, Brian A. Van Tine

et al.

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

Published: April 12, 2025

Osteosarcoma (OS) is a rapidly progressive primary malignant bone tumor that occurs in children and adolescents aged between 15 19 years adults over 60 years. As alternative splicing (AS) changes caused by abnormal factors contribute to progression, gene expression AS analyses were performed on 44 osteosarcoma patients create genome-wide co-expression network of RNA-binding proteins (RBPs), events, genes. A gain- or loss-of-function cell model was established, an interactive analysis enrichment performed. Karyopherin Subunit Alpha 2 (KPNA2) negatively correlated with patient survival. KPNA2 transports factor Y-box Binding Protein 1 (YBX1) into the nucleus YBX1 accelerates degradation ATP-dependent RNA helicase DDX3X (DDX3X) through nonsense-mediated decay (NMD) pathway promote intron retention gene, thus reducing protein levels. KPNA2/YBX1 axis regulates stability mRNA cycle progression. KPNA2/YBX1/DDX3X might be potential targets for inhibiting disease progression improving OS It integrates control represents prognostic biomarker therapeutic target therapy.

Language: Английский

Citations

0
G3BP-driven RNP granules promote inhibitory RNA-RNA interactions resolved by DDX3X to regulate mRNA translatability DOI Creative Commons

Irmela R. E. A. Trussina,

Andreas Hartmann, Christine Desroches Altamirano

et al.

Molecular Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Ribonucleoprotein (RNP) granules have been linked to translation regulation and disease, but their assembly regulatory mechanisms are not well understood. Here, we show that the RNA-binding protein G3BP1 preferentially interacts with unfolded RNA, driving of RNP granule-like condensates establish RNA-RNA interactions. These interactions limit mobility translatability sequestered mRNAs stabilize condensates. The DEAD-box RNA helicase DDX3X attenuates inside condensates, rendering dynamic enabling mRNA translation. Importantly, disease-associated catalytically inactive variants fail resolve such Inhibiting in cultured cells accelerates granule delays disassembly, indicating contribute stability cells. Our findings reveal how generate inhibitory modulated by helicases ensure availability translatability.

Language: Английский

Citations

3
tRNA-derived fragment 3′tRF-AlaAGC modulates cell chemoresistance and M2 macrophage polarization via binding to TRADD in breast cancer DOI Creative Commons
Dongping Mo, Xun Tang, Yuyan Ma

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 30, 2024

Abstract Background Drug resistance, including Adriamycin-based therapeutic remains a challenge in breast cancer (BC) treatment. Studies have revealed that macrophages could play pivotal role mediating the chemoresistance of cells. Accumulating evidence suggests tRNA-Derived small RNAs (tDRs) are associated physiological and pathological processes multiple cancers. However, underlying mechanisms tDRs on BC tumor-associated remain largely unknown. Methods The high-throughput sequencing technique was used to screen expression profile Gain- loss-of-function experiments xenograft models were performed verify biological function 3′tRF-Ala-AGC CIBERSORT algorithm investigate immune cell infiltration tissues. To explore macrophages, M2 transfected with mimic or inhibitor co-cultured Effects Nuclear factor-κb (NF-κb) pathway investigated by NF-κb nuclear translocation assay western blot analysis. RNA pull-down identify interacting proteins. Results A 3′tRF fragment 3′tRF-AlaAGC screened, which is significantly overexpressed specimens Adriamycin-resistant promote malignant activity facilitate polarization vitro vivo. Higher more likely lymph node metastasis deeper invasion patients. Mechanistically, binds Type 1-associated death domain protein (TRADD) cells, suppression TRADD partially abolished enhanced effect phenotype M2. signaling activated cells mimic. Conclusions might modulate macrophage via binding increase promoting through pathway.

Language: Английский

Citations

2
Prostatic androgen receptor signaling shows an age-related and lobe-specific alteration in mice DOI Creative Commons
Han Zhang, Teresa T. Liu, Emily A. Ricke

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Dec. 5, 2024

Benign prostatic hyperplasia (BPH) is an age-related disease that affects millions of aging males globally. While the pathogenesis BPH remains incompletely understood, emerging evidence suggests a pivotal role for androgen receptor (AR) in mediating prostate growth and function. Understanding AR signaling alteration may inform novel treatments. Here, we analyzed protein expressions AR, NKX3.1, Ki-67 young (2 months) aged (24 mice. We also examined potential mechanism expression. Compared to mice, decreased NKX3.1 expression was observed anterior (AP) ventral (VP) indicating reduced these lobes. Additionally, proliferation maker AP, VP, dorsal-lateral (DLP), with no difference apoptosis as compared counterparts. conclude shows lobe-specific

Language: Английский

Citations

1
Cell-Free Analysis Reveals the Role of RG/RGG Motifs in DDX3X Phase Separation and Their Potential Link to Cancer Pathogenesis DOI Open Access
Hongran Chen, Boyang Li, Xinyue Zhao

et al.

Published: May 2, 2024

The DEAD-box RNA helicase DDX3X is a multifunctional protein involved in metabolism and stress responses. In this study, we investigated the role of RG/RGG motifs dynamic process liquid-liquid phase separation (LLPS) using cell-free assays explored their potential link to cancer development through bioinformatic analysis. Our results demonstrate that number, location, composition significantly influence ability undergo form self-aggregates. Mutational analysis revealed spacing between number glycine residues within each motif are critical factors determining extent separation. Bioinformatic genomic datasets uncovered significant enrichment mutations across multiple types, particularly N-terminal region protein. Furthermore, found co-expressed with granule G3BP1 several types can co-phase system, suggesting functional interaction these proteins phase-separated structures. may interact domains subsequently exert important cellular functions under situation. Collectively, our findings provide novel insights into modulating contribution pathogenesis.

Language: Английский

Citations

0
Cell-free analysis reveals the role of RG/RGG motifs in DDX3X phase separation and their potential link to cancer pathogenesis DOI
Hongran Chen, Boyang Li, Xinyue Zhao

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 279, P. 135251 - 135251

Published: Aug. 31, 2024

Language: Английский

Citations

0
Enhancement of Stress Granule Formation by a Chiral Compound Targeting G3BP1 via eIF2α Phosphorylation DOI Open Access

Yoon Ho Park,

Hyun Suh Cho,

Sungjin Moon

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10571 - 10571

Published: Sept. 30, 2024

The chirality of a chemical differentiates it from its mirror-image counterpart. This unique property has significant implications in chemistry, biology, and drug discovery, where chiral chemicals display high selectivity activity achieving target specificity reducing attrition rates development. Stress granules (SGs) are dynamic assemblies proteins RNA that form the cytoplasm cells under stress conditions. Modulating their formation or disassembly could offer novel approach to treating wide range diseases. led interest SGs as potential therapeutic targets. study examined NTF2-like domain G3BP1 possible for SG modulation. Molecular docking was used simulate interactions compounds with domain, candidate structure identified. experiments showed compound induced SG-like granules. Importantly, ability this modulate offers valuable insights into new mechanism underlying dynamics promoting assembly SGs, mechanism, turn, holds development drugs diverse mechanisms action potentially synergistic effects.

Language: Английский

Citations

0
G-quadruplex DNA and RNA in cellular senescence DOI Creative Commons

Rocio Diaz Escarcega,

Paul R. Marshall, Andrey S. Tsvetkov

et al.

Frontiers in Aging, Journal Year: 2024, Volume and Issue: 5

Published: Oct. 9, 2024

Normal cells divide, are damaged, and repaired across their lifetime. As age, they enter cellular senescence, characterized by a permanent state of cell-cycle arrest triggered various stressors. The molecular mechanisms that regulate senescent phenotypes have been actively investigated over the last several decades; however, one area has neglected is how G-quadruplex (G4) DNA RNA (G4-DNA G4-RNA) mediate senescence. These non-canonical four-stranded structures most normative RNA-dependent processes, such as transcription, replication, translation, well pathogenic mechanisms, including genomic instability abnormal stress granule function. This review also highlights contribution G4s to sex differences in age-associated diseases emphasizes potential translational approaches target senescence anti-aging through G4 manipulation.

Language: Английский

Citations

0