The DEAD-box helicase eIF4A1 acts as RNA chaperone during mitotic exit enabling chromatin decondensation DOI Creative Commons
Wolfram Antonin, Ramona Jühlen,

Sabine C. Wiesmann

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 20, 2024

Abstract During mitosis, chromosomes condense and decondense to segregate faithfully undamaged. The exact molecular mechanisms are not well understood. We identify the DEAD-box helicase eIF4A1 as a critical factor in this process. In cell-free condensation assay is crucial for process, relying on its RNA-binding ability but ATPase activity. Reducing levels cells consistently slows down chromatin decondensation during nuclear reformation. Conversely, increasing concentration mitotic accelerates their decondensation. absence of affects perichromatin layer, which surrounds mitosis consists RNA mainly nucleolar proteins. vitro, acts an chaperone, dissociating biomolecular condensates chaperone activity required regulate composition fluidity dynamic reorganization exit mitosis.

Language: Английский

Formation, function, and pathology of RNP granules DOI Creative Commons
Nina Ripin,

Roy Parker

Cell, Journal Year: 2023, Volume and Issue: 186(22), P. 4737 - 4756

Published: Oct. 1, 2023

Language: Английский

Citations

80
RNA granules in neuronal plasticity and disease DOI Open Access

Karl E. Bauer,

Bruna R. de Queiroz, Michael Kiebler

et al.

Trends in Neurosciences, Journal Year: 2023, Volume and Issue: 46(7), P. 525 - 538

Published: May 16, 2023

Language: Английский

Citations

28
The Story of RNA Unfolded: The Molecular Function of DEAD- and DExH-Box ATPases and Their Complex Relationship with Membraneless Organelles DOI
Kerstin Dörner, Maria Hondele

Annual Review of Biochemistry, Journal Year: 2024, Volume and Issue: 93(1), P. 79 - 108

Published: April 10, 2024

DEAD- and DExH-box ATPases (DDX/DHXs) are abundant highly conserved cellular enzymes ubiquitously involved in RNA processing. By remodeling RNA–RNA RNA–protein interactions, they often function as gatekeepers that control the progression of diverse maturation steps. Intriguingly, most DDX/DHXs localize to membraneless organelles (MLOs) such nucleoli, nuclear speckles, stress granules, or processing bodies. Recent findings suggest not only localization MLOs can promote interaction between their targets but also key regulators MLO formation turnover through condensation ATPase activity.In this review, we describe molecular ribosome biogenesis, messenger splicing, export, translation, storage decay well association with prominent MLOs. We discuss how enzymatic is linked DDX/DHX condensation, accumulation ribonucleoprotein particles dynamics. Future research will reveal these processes orchestrate life cycle space time.

Language: Английский

Citations

9
A comprehensive review on DDX3X liquid phase condensation in health and neurodevelopmental disorders DOI
Ivan Rosa e Silva, Juliana Helena Costa Smetana, Juliana Ferreira de Oliveira

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 259, P. 129330 - 129330

Published: Jan. 11, 2024

Language: Английский

Citations

6
Interferon-α stimulates DExH-box helicase 58 to prevent hepatocyte ferroptosis DOI Creative Commons

Kaiwei Jia,

Ren-qi Yao, Yiwen Fan

et al.

Military Medical Research, Journal Year: 2024, Volume and Issue: 11(1)

Published: April 15, 2024

Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and frequently observed war wounds trauma. Hepatocyte ferroptosis plays a critical role in I/R injury, however, it remains unclear whether this process controlled or regulated members of the DEAD/DExH-box helicase (DDX/DHX) family. The expression DDX/DHX family was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, partial operation performed. Single-cell RNA sequencing (scRNA-seq) post suggested enhanced Dhx58hep-/-. mRNAs proteins associated with DExH-box 58 (DHX58) immunoprecipitation-sequencing (RIP-seq) IP-mass spectrometry (IP-MS). Excessive production reactive oxygen species (ROS) decreased IFN-stimulated gene hepatocytes promoted ferroptosis, while treatment IFN-α increased DHX58 prevented injury. Mechanistically, RNA-binding activity constitutively associates mRNA glutathione peroxidase 4 (GPX4), central suppressor, recruits m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote translation Gpx4 an m6A-dependent manner, thus enhancing GPX4 protein levels preventing ferroptosis. This study provides mechanistic evidence that stimulates m6A-modified mRNA, suggesting potential clinical application prevention

Language: Английский

Citations

6
Phase separation in cancer at a glance DOI Creative Commons

Qingqing Xie,

Jiejuan Cheng,

Wuxuan Mei

et al.

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: April 1, 2023

Abstract Eukaryotic cells are segmented into multiple compartments or organelles within the cell that regulate distinct chemical and biological processes. Membrane-less membrane-less microscopic cellular contain protein RNA molecules perform a wide range of functions. Liquid–liquid phase separation (LLPS) can reveal how develop via dynamic biomolecule assembly. LLPS either segregates undesirable from aggregates desired ones in cells. Aberrant results production abnormal biomolecular condensates (BMCs), which cause cancer. Here, we explore intricate mechanisms behind formation BMCs its biophysical properties. Additionally, discuss recent discoveries related to tumorigenesis, including aberrant signaling transduction, stress granule formation, evading growth arrest, genomic instability. We also therapeutic implications Understanding concept mechanism role tumorigenesis is crucial for antitumor strategies.

Language: Английский

Citations

15
DEAD/DEAH-box RNA helicases shape the risk of neurodevelopmental disorders DOI

Chiara Fiorenzani,

Adele Mossa,

Silvia De Rubeis

et al.

Trends in Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
The DEAD-box helicase eIF4A1/2 acts as RNA chaperone during mitotic exit enabling chromatin decondensation DOI Creative Commons
Ramona Jühlen,

Sabine C. Wiesmann,

Anja Scheufen

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 11, 2025

Abstract During mitosis, chromosomes condense and decondense to segregate faithfully undamaged. The exact molecular mechanisms are not well understood. We identify the DEAD-box helicase eIF4A1/2 as a critical factor in this process. In cell-free condensation assay is crucial for process, relying on its RNA-binding ability but ATPase activity. Reducing levels cells consistently slows down chromatin decondensation during nuclear reformation. Conversely, increasing concentration mitotic accelerates their decondensation. absence of affects perichromatin layer, which surrounds mitosis consists RNA mainly nucleolar proteins. vitro, acts an chaperone, dissociating biomolecular condensates chaperone activity required regulate composition fluidity dynamic reorganization exit mitosis.

Language: Английский

Citations

0
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

10
Me31B: a key repressor in germline regulation and beyond DOI Open Access
Ming Gao

Bioscience Reports, Journal Year: 2024, Volume and Issue: 44(5)

Published: April 12, 2024

Maternally Expressed at 31B (Me31B), an evolutionarily conserved ATP-dependent RNA helicase, plays important role in the development of germline across diverse animal species. Its cellular functionality has been posited as a translational repressor, participating various metabolism pathways to intricately regulate spatiotemporal expression RNAs. Despite its evident significance, precise and mechanistic underpinnings Me31B remain insufficiently understood. This article endeavors comprehensively review historic recent research on Me31B, distill major findings, discern generalizable patterns Me31B's functions different contexts, provide insights into fundamental mechanism action. The primary focus this centers elucidating Drosophila within germline, while concurrently delving pertinent orthologs other species systems.

Language: Английский

Citations

3