Current Opinion in Cell Biology, Journal Year: 2025, Volume and Issue: 93, P. 102480 - 102480
Published: Feb. 12, 2025
Language: Английский
Cell, Journal Year: 2024, Volume and Issue: 187(8), P. 1889 - 1906.e24
Published: March 18, 2024
Nucleoli are multicomponent condensates defined by coexisting sub-phases. We identified distinct intrinsically disordered regions (IDRs), including acidic (D/E) tracts and K-blocks interspersed E-rich regions, as defining features of nucleolar proteins. show that the localization preferences proteins determined their IDRs types RNA or DNA binding domains they encompass. In vitro reconstitutions studies in cells showed how condensation, which combines complex coacervation components, contributes to organization. D/E contribute lowering pH co-condensates formed with RNAs vitro. cells, this sets up a gradient between nucleoli nucleoplasm. By contrast, juxta-nucleolar bodies, have different macromolecular compositions, featuring protein very charge profiles, values equivalent higher than Our findings compositional specificities generate physicochemical properties for condensates.
Language: Английский
Citations
65
Cell, Journal Year: 2024, Volume and Issue: 187(19), P. 5282 - 5297.e20
Published: Aug. 20, 2024
Biomolecular condensates assemble in living cells through phase separation and related transitions. An underappreciated feature of these dynamic molecular assemblies is that they form interfaces with other cellular structures, including membranes, cytoskeleton, DNA RNA, membraneless compartments. These are expected to give rise capillary forces, but there few ways quantifying harnessing forces cells. Here, we introduce viscoelastic chromatin tethering organization (VECTOR), which uses light-inducible biomolecular generate at targeted loci. VECTOR can be utilized programmably reposition genomic loci on a timescale seconds minutes, quantitatively revealing local heterogeneity the material properties chromatin. synthetic built from components naturally liquid-like structures cells, highlighting potential role for native do work reorganize genome impact architecture.
Language: Английский
Citations
24
Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(3), P. 438 - 449
Published: Feb. 12, 2024
Language: Английский
Citations
21
Nucleus, Journal Year: 2024, Volume and Issue: 15(1)
Published: March 5, 2024
In higher eukaryotes, the nucleolus harbors at least three sub-phases that facilitate multiple functionalities including ribosome biogenesis. The prominent coexisting are fibrillar center (FC), dense component (DFC), and granular (GC). Here, we review recent efforts in profiling sub-phase compositions shed light on types of physicochemical properties emerge from compositional biases territorial organization specific macromolecules. We highlight roles played by molecular grammars which refers to protein sequence features substrate binding domains, intrinsically disordered regions, multivalence these distinct domains / regions. introduce concept a barcode emergent nucleoli. Although our knowledge full remains incomplete, hope prompts investigations into undiscovered engenders an appreciation for how why unique microenvironments control biochemical reactions
Language: Английский
Citations
21
Molecular Cell, Journal Year: 2025, Volume and Issue: 85(2), P. 290 - 308
Published: Jan. 1, 2025
Language: Английский
Citations
3
Science, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 6, 2025
Cells have evolved mechanisms to distribute ~10 billion protein molecules subcellular compartments where diverse proteins involved in shared functions must assemble. Here, we demonstrate that with share amino acid sequence codes guide them compartment destinations. A language model, ProtGPS, was developed predicts high performance the localization of human excluded from training set. ProtGPS successfully guided generation novel sequences selectively assemble nucleolus. identified pathological mutations change this code and lead altered proteins. Our results indicate contain not only a folding code, but also previously unrecognized governing their distribution compartments.
Language: Английский
Citations
3
Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 168953 - 168953
Published: Jan. 1, 2025
Language: Английский
Citations
2
Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 25(4), P. 309 - 332
Published: Dec. 11, 2023
Language: Английский
Citations
38
Molecular Cell, Journal Year: 2023, Volume and Issue: 84(2), P. 194 - 201
Published: Nov. 27, 2023
In eukaryotic genomes, transcriptional machinery and nucleosomes compete for binding to DNA sequences; thus, a crucial aspect of gene regulatory element function is modulate chromatin accessibility transcription factor (TF) RNA polymerase binding. Recent structural studies have revealed multiple modes TF engagement with nucleosomes, but how initial "pioneering" results in steady-state further II (RNAPII) has been unclear. Even less well understood distant sites open interact one another, such as when developmental enhancers activate promoters release RNAPII productive elongation. Here, we review evidence the centrality conserved SWI/SNF family nucleosome remodeling complexes, both pioneering mediating enhancer-promoter contacts. Consideration unwrapping ATP hydrolysis activities together their architectural features, may reconcile occupancy rapid dynamics observed by live imaging.
Language: Английский
Citations
24
Journal of Molecular Biology, Journal Year: 2024, Volume and Issue: 436(7), P. 168453 - 168453
Published: Jan. 22, 2024
Language: Английский
Citations
11