Shell protein composition specified by the lncRNA NEAT1 domains dictates the formation of paraspeckles as distinct membraneless organelles

Nature Cell Biology, Journal Year: 2023, Volume and Issue: 25(11), P. 1664 - 1675

Published: Nov. 1, 2023

Language: Английский

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Molecular mechanisms of schizophrenia: Insights from human genetics

Current Opinion in Neurobiology, Journal Year: 2023, Volume and Issue: 81, P. 102731 - 102731

Published: May 26, 2023

Schizophrenia is a debilitating psychiatric disorder that affects millions of people worldwide; however, its etiology poorly understood at the molecular and neurobiological levels. A particularly important advance in recent years discovery rare genetic variants associated with greatly increased risk developing schizophrenia. These primarily loss-of-function are found genes overlap those implicated by common involved regulation glutamate signaling, synaptic function, DNA transcription, chromatin remodeling. Animal models harboring mutations these large-effect schizophrenia show promise providing additional insights into mechanisms disease.

Language: Английский

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Genome-wide analysis of the interplay between chromatin-associated RNA and 3D genome organization in human cells

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

Published: Oct. 16, 2023

Abstract The interphase genome is dynamically organized in the nucleus and decorated with chromatin-associated RNA (caRNA). It remains unclear whether architecture modulates spatial distribution of caRNA vice versa. Here, we generate a resource genome-wide RNA-DNA DNA-DNA contact maps human cells. These reveal chromosomal domains demarcated by locally transcribed RNA, hereafter termed RNA-defined domains. Further, spreading constrained boundaries topologically associating (TADs), demonstrating role 3D structure modulating RNA. Conversely, stopping transcription or acute depletion induces thousands chromatin loops genome-wide. Activation suppression specific genes suppresses creates straddling these genes. Deletion caRNA-producing genomic sequence promotes that straddle interchromosomal target sequences this caRNA. data suggest feedback loop where which turn affects dynamic organization.

Language: Английский

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SRRM2 phase separation drives assembly of nuclear speckle subcompartments

Cell Reports, Journal Year: 2024, Volume and Issue: 43(3), P. 113827 - 113827

Published: Feb. 20, 2024

Nuclear speckles (NSs) are nuclear biomolecular condensates that postulated to form by macromolecular phase separation, although the detailed underlying forces driving NS formation remain elusive. SRRM2 and SON 2 non-redundant scaffold proteins for NSs. How each individual protein governs assembly of network functional relationship between largely unknown. Here, we uncover immiscible multiphases within functionally independent, specifically regulating alternative splicing subsets mRNA targets, respectively. We further show forms multicomponent liquid phases in cells drive subcompartmentalization, which is reliant on homotypic interaction heterotypic non-selective protein-RNA complex coacervation-driven separation. serine/arginine-rich (RS) domains higher-order oligomers can be replaced oligomerizable synthetic modules. The serine residues RS domains, however, play an irreplaceable role fine-tuning liquidity

Language: Английский

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The Story of RNA Unfolded: The Molecular Function of DEAD- and DExH-Box ATPases and Their Complex Relationship with Membraneless Organelles

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

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