SON and SRRM2 are essential for nuclear speckle formation DOI Creative Commons
İbrahim Ilik, Michał Małszycki,

Anna Katharina Lübke

et al.

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Oct. 23, 2020

Nuclear speckles (NS) are among the most prominent biomolecular condensates. Despite their prevalence, research on function of NS is virtually restricted to colocalization analyses, since an organizing core, without which cannot form, remains unidentified. The monoclonal antibody SC35, raised against a spliceosomal extract, frequently used mark NS. Unexpectedly, we found that this was mischaracterized and main target SC35 mAb SRRM2, spliceosome-associated protein sharply localizes Here show that, core likely formed by SON depletion leads only partial disassembly NS, while co-depletion SRRM2 or in cell-line where intrinsically disordered regions (IDRs) genetically deleted, near-complete dissolution This work, therefore, paves way study role under diverse physiological stress conditions.

Language: Английский

A framework for understanding the functions of biomolecular condensates across scales DOI
Andrew S. Lyon, William B. Peeples, Michael K. Rosen

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2020, Volume and Issue: 22(3), P. 215 - 235

Published: Nov. 9, 2020

Language: Английский

Citations

686

Organization and regulation of gene transcription DOI
Patrick Cramer

Nature, Journal Year: 2019, Volume and Issue: 573(7772), P. 45 - 54

Published: Aug. 28, 2019

Language: Английский

Citations

618

Alternative Splicing Regulatory Networks: Functions, Mechanisms, and Evolution DOI Creative Commons
Jernej Ule, Benjamin J. Blencowe

Molecular Cell, Journal Year: 2019, Volume and Issue: 76(2), P. 329 - 345

Published: Oct. 1, 2019

Language: Английский

Citations

615

The Self-Organizing Genome: Principles of Genome Architecture and Function DOI Creative Commons
Tom Misteli

Cell, Journal Year: 2020, Volume and Issue: 183(1), P. 28 - 45

Published: Sept. 24, 2020

Language: Английский

Citations

558

Evaluating phase separation in live cells: diagnosis, caveats, and functional consequences DOI Open Access
David T. McSwiggen, Mustafa Mir, Xavier Darzacq

et al.

Genes & Development, Journal Year: 2019, Volume and Issue: 33(23-24), P. 1619 - 1634

Published: Oct. 8, 2019

The idea that liquid–liquid phase separation (LLPS) may be a general mechanism by which molecules in the complex cellular milieu self-organize has generated much excitement and fervor cell biology community. While this concept is not new, its rise to preeminence resulted renewed interest mechanisms shape drive diverse self-assembly processes from gene expression division stress responses. In vitro biochemical data have been instrumental deriving some of fundamental principles molecular grammar biological separate, basis these interactions. Definitive evidence lacking as whether same apply physiological environment inside living cells. Perspective, we analyze supporting vivo across multiple processes. We find for LLPS often phenomenological inadequate discriminate between other possible mechanisms. Moreover, causal relationship functional consequences are even more elusive. underscore importance performing quantitative measurements on proteins their endogenous state abundance, well make recommendations experiments yield conclusive results.

Language: Английский

Citations

543

A conceptual framework for understanding phase separation and addressing open questions and challenges DOI Creative Commons
Tanja Mittag, Rohit V. Pappu

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(12), P. 2201 - 2214

Published: June 1, 2022

Language: Английский

Citations

500

RNA-Mediated Feedback Control of Transcriptional Condensates DOI Creative Commons
Jonathan E. Henninger, Ozgur Oksuz, Krishna Shrinivas

et al.

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

Published: Dec. 16, 2020

Language: Английский

Citations

454

Liquid–liquid phase separation in human health and diseases DOI Creative Commons
Bin Wang, Lei Zhang, Tong Dai

et al.

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

Citations

450

Partitioning of cancer therapeutics in nuclear condensates DOI
Isaac A. Klein, Ann Boija,

Lena K. Afeyan

et al.

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

Citations

417

Biomolecular Condensates in the Nucleus DOI Creative Commons
Benjamin R. Sabari, Alessandra Dall’Agnese,

Richard A. Young

et al.

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

Published: July 17, 2020

Language: Английский

Citations

362