RNA-Mediated Feedback Control of Transcriptional Condensates

Cell, Journal Year: 2020, Volume and Issue: 184(1), P. 207 - 225.e24

Published: Dec. 16, 2020

Language: Английский

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Liquid–liquid phase separation in human health and diseases

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Aug. 1, 2021

Abstract Emerging evidence suggests that liquid–liquid phase separation (LLPS) represents a vital and ubiquitous phenomenon underlying the formation of membraneless organelles in eukaryotic cells (also known as biomolecular condensates or droplets). Recent studies have revealed evidences indicate LLPS plays role human health diseases. In this review, we describe our current understanding summarize its physiological functions. We further development Additionally, review recently developed methods for studying LLPS. Although research is infancy—but fast-growing—it clear an essential pathophysiological conditions. This highlights need overview recent advances field to translate knowledge regarding into therapeutic discoveries.

Language: Английский

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Partitioning of cancer therapeutics in nuclear condensates

Science, Journal Year: 2020, Volume and Issue: 368(6497), P. 1386 - 1392

Published: June 18, 2020

Drug partitioning in nuclear condensates There is increasing interest the function of phase-separated biomolecular cells because their distinct properties and expanding roles important biological processes. Klein et al. considered fate small-molecule therapeutics context (see Perspective by Viny Levine). They show that certain antineoplastic drugs have physicochemical cause them to concentrate preferentially condensates, both vitro cancer cells. This property influences drug activity, protein mutations alter condensate formation can lead resistance. Optimizing may be valuable developing improved therapeutics. Science , this issue p. 1386 ; see also 1314

Language: Английский

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Nucleocapsid protein of SARS-CoV-2 phase separates into RNA-rich polymerase-containing condensates

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Nov. 27, 2020

The etiologic agent of the Covid-19 pandemic is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). viral membrane SARS-CoV-2 surrounds a helical nucleocapsid in which genome encapsulated by protein. protein produced at high levels within infected cells, enhances efficiency RNA transcription, and essential for replication. Here, we show that induces cooperative liquid-liquid phase separation In agreement with its ability to separate vitro, associates cells stress granules, cytoplasmic RNA/protein granules form through are modulated viruses maximize replication efficiency. Liquid-liquid generates high-density protein/RNA condensates recruit RNA-dependent polymerase complex providing mechanism efficient transcription RNA. Inhibition RNA-induced small molecules or biologics thus can interfere key step cycle.

Language: Английский

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Biomolecular Condensates in the Nucleus

Trends in Biochemical Sciences, Journal Year: 2020, Volume and Issue: 45(11), P. 961 - 977

Published: July 17, 2020

Language: Английский

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Mechanisms of enhancer action: the known and the unknown

Genome biology, Journal Year: 2021, Volume and Issue: 22(1)

Published: April 15, 2021

Abstract Differential gene expression mechanisms ensure cellular differentiation and plasticity to shape ontogenetic phylogenetic diversity of cell types. A key regulator differential programs are the enhancers, gene-distal cis -regulatory sequences that govern spatiotemporal quantitative dynamics target genes. Enhancers widely believed physically contact promoters effect transcriptional activation. However, our understanding full complement regulatory proteins definitive mechanics enhancer action is incomplete. Here, we review recent findings present some emerging concepts on also outline a set outstanding questions.

Language: Английский

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Liquid-liquid phase separation in biology: mechanisms, physiological functions and human diseases

Science China Life Sciences, Journal Year: 2020, Volume and Issue: 63(7), P. 953 - 985

Published: April 30, 2020

Language: Английский

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The relationship between genome structure and function

Nature Reviews Genetics, Journal Year: 2020, Volume and Issue: 22(3), P. 154 - 168

Published: Nov. 24, 2020

Language: Английский

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The epigenetic basis of cellular heterogeneity

Nature Reviews Genetics, Journal Year: 2020, Volume and Issue: 22(4), P. 235 - 250

Published: Nov. 26, 2020

Language: Английский

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Structure and mechanism of the RNA polymerase II transcription machinery

Genes & Development, Journal Year: 2020, Volume and Issue: 34(7-8), P. 465 - 488

Published: April 1, 2020

RNA polymerase II (Pol II) transcribes all protein-coding genes and many noncoding RNAs in eukaryotic genomes. Although Pol is a complex, 12-subunit enzyme, it lacks the ability to initiate transcription cannot consistently transcribe through long DNA sequences. To execute these essential functions, an array of proteins protein complexes interact with regulate its activity. In this review, we detail structure mechanism over dozen factors that govern initiation (e.g., TFIID, TFIIH, Mediator), pausing, elongation DSIF, NELF, PAF, P-TEFb). The structural basis for regulation has advanced rapidly past decade, largely due technological innovations cryoelectron microscopy. Here, summarize wealth functional data have enabled deeper understanding mechanisms; also highlight mechanistic questions remain unanswered or controversial.

Language: Английский

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