RNA granules: functional compartments or incidental condensates?

Genes & Development, Journal Year: 2023, Volume and Issue: 37(9-10), P. 354 - 376

Published: May 1, 2023

RNA granules are mesoscale assemblies that form in the absence of limiting membranes. contain factors for biogenesis and turnover often assumed to represent specialized compartments biochemistry. Recent evidence suggests assemble by phase separation subsoluble ribonucleoprotein (RNP) complexes partially demix from cytoplasm or nucleoplasm. We explore possibility some nonessential condensation by-products arise when RNP exceed their solubility limit as a consequence cellular activity, stress, aging. describe use evolutionary mutational analyses single-molecule techniques distinguish functional "incidental condensates."

Language: Английский

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Enhancer selectivity in space and time: from enhancer–promoter interactions to promoter activation

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(7), P. 574 - 591

Published: Feb. 27, 2024

Language: Английский

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iU-ExM: nanoscopy of organelles and tissues with iterative ultrastructure expansion microscopy

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 30, 2023

Expansion microscopy (ExM) is a highly effective technique for super-resolution fluorescence that enables imaging of biological samples beyond the diffraction limit with conventional microscopes. Despite development several enhanced protocols, ExM has not yet demonstrated ability to achieve precision nanoscopy techniques such as Single Molecule Localization Microscopy (SMLM). Here, address this limitation, we have developed an iterative ultrastructure expansion (iU-ExM) approach achieves SMLM-level resolution. With iU-ExM, it now possible visualize molecular architecture gold-standard samples, eight-fold symmetry nuclear pores or organization conoid in Apicomplexa. its wide-ranging applications, from isolated organelles cells and tissue, iU-ExM opens new avenues scientists studying structures functions.

Language: Английский

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Transcriptional condensates: a blessing or a curse for gene regulation?

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Feb. 16, 2024

Whether phase-separation is involved in the organization of transcriptional machinery and if it aids or inhibits process a matter intense debate. In this Mini Review, we will cover current knowledge regarding role condensates on gene expression regulation. We summarize latest discoveries relationship between condensate formation, genome organization, activity, focusing strengths weaknesses experimental approaches used to interrogate these aspects transcription living cells. Finally, discuss challenges for future research.

Language: Английский

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Microglial-derived C1q integrates into neuronal ribonucleoprotein complexes and impacts protein homeostasis in the aging brain

Cell, Journal Year: 2024, Volume and Issue: 187(16), P. 4193 - 4212.e24

Published: June 27, 2024

Language: Английский

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The dark side of fluorescent protein tagging – the impact of protein tags on biomolecular condensation

Molecular Biology of the Cell, Journal Year: 2025, Volume and Issue: 36(3)

Published: Jan. 29, 2025

Biomolecular condensation has emerged as an important mechanism to control various cellular processes through the formation of membraneless organelles. Fluorescent protein tags have been extensively used study and properties condensates in vitro vivo, but there is evidence that may perturb proteins. In this study, we carefully assess effects on yeast DEAD-box ATPase Dhh1, a central regulator processing bodies (P-bodies), which are biomolecular involved mRNA metabolism. We show fluorescent well polyhistidine tag greatly affect Dhh1 lead with different dynamic properties. Tagging proteins vivo alters number P-bodies upon glucose starvation some even constitutive nonstressed cells. These data raise concerns about accuracy tagged experiments, highlighting need for caution when interpreting results.

Language: Английский

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m6A governs length-dependent enrichment of mRNAs in stress granules

Nature Structural & Molecular Biology, Journal Year: 2023, Volume and Issue: 30(10), P. 1525 - 1535

Published: Sept. 14, 2023

Language: Английский

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Transcriptional condensates and phase separation: condensing information across scales and mechanisms

Nucleus, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 22, 2023

Transcription is the fundamental process of gene expression, which in eukaryotes occurs within complex physicochemical environment nucleus. Decades research have provided extreme detail molecular and functional mechanisms transcription, but spatial genomic organization transcription remains mysterious. Recent discoveries show that transcriptional components can undergo phase separation create distinct compartments inside nucleus, providing new models through to view eukaryotes. In this review, we focus on condensates their separation-like behaviors. We suggest differentiation between physical descriptions dynamic biomolecular assemblies required for productive discuss how are central organizing three-dimensional genome across temporal scales. Finally, map approaches therapeutic manipulation ask what technical advances needed understand more completely.

Language: Английский

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Transcription decouples estrogen-dependent changes in enhancer-promoter contact frequencies and spatial proximity

PLoS Genetics, Journal Year: 2024, Volume and Issue: 20(5), P. e1011277 - e1011277

Published: May 23, 2024

How enhancers regulate their target genes in the context of 3D chromatin organization is extensively studied and models which do not require direct enhancer-promoter contact have recently emerged. Here, we use activation estrogen receptor-dependent a breast cancer cell line to study communication at two loci. This allows high temporal resolution tracking molecular events from hormone stimulation efficient gene activation. We examine how both spatial proximity assayed by DNA fluorescence situ hybridization, frequencies resulting fragmentation ligation, change dynamically during enhancer-driven These orthogonal methods produce seemingly paradoxical results: upon enhancer increase while decreases. explore this apparent discrepancy using different receptor ligands transcription inhibitors. Our data demonstrate that are independent whereas altered depends on transcription. results emphasize relationship between physical distance nucleus, especially over short genomic distances, always simple one.

Language: Английский

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YAP condensates are highly organized hubs

iScience, Journal Year: 2024, Volume and Issue: 27(6), P. 109927 - 109927

Published: May 7, 2024

YAP/TEAD signaling is essential for organismal development, cell proliferation, and cancer progression. As a transcriptional coactivator, how YAP activates its downstream target genes incompletely understood. forms biomolecular condensates in response to hyperosmotic stress, concentrating transcription-related factors activate genes. However, whether under other signals, organize function, transcription general are unknown. Here, we report that endogenous sub-micron scale Hippo pathway regulation actin cytoskeletal tension. stabilized by the factor TEAD1, recruit BRD4, coactivator enriched at active enhancers. Using single-particle tracking, found slowed diffusion within condensate boundaries, possible mechanism promoting search. These results reveal formation highly regulated process critical gene expression.

Language: Английский

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