p53 mediates target gene association with nuclear speckles for amplified RNA expression

Alexander, Katherine A.; Coté, Allison; Nguyen, Son C.; Zhang, L; Gholamalamdari, Omid; Agudelo-Garcia, Paula A.; Lin-Shiao, Enrique; Tanim, K M Ahasan Al; Lim, Joan; Biddle, Nicolas; Dunagin, Margaret C.; Good, Charly R.; Mendoza, Mariel; Little, Shawn C.; Belmont, Andrew S.; Joyce, Eric F.; Raj, Arjun; Berger, Shelley L.

doi:10.1016/j.molcel.2021.03.006

Cited by 61 publications

(72 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Examples Of Biomolecular Condensates With Internal Architecturementioning

confidence: 99%

“…Nuclear speckles, like paraspeckles, are a nuclear condensate composed of RNA and protein [ 33 , 144 , 145 ]. Nuclear speckles participate in mRNA transcription, splicing, and processing, and are identified by the presence of phosphorylated serine-arginine (SR)-family splicing regulators like SC35 (SRSF2) and the splicing co-activator SRRM2 [ 33 , 145 ]. More detailed research into the structure of demixed nuclear speckles uncovered that mRNA tends to be further from the centre of the nuclear speckle, leading to the hypothesis that nuclear speckles have a proteinaceous core surrounded by an RNA shell [ 33 ].…”

Section: Examples Of Biomolecular Condensates With Internal Architecturementioning

confidence: 99%

See 1 more Smart Citation

Higher-order organization of biomolecular condensates

et al. 2021

View full text Add to dashboard Cite

A guiding principle of biology is that biochemical reactions must be organized in space and time. One way this spatio-temporal organization is achieved is through liquid–liquid phase separation (LLPS), which generates biomolecular condensates. These condensates are dynamic and reactive, and often contain a complex mixture of proteins and nucleic acids. In this review, we discuss how underlying physical and chemical processes generate internal condensate architectures. We then outline the diverse condensate architectures that are observed in biological systems. Finally, we discuss how specific condensate organization is critical for specific biological functions.

show abstract

Section: Examples Of Biomolecular Condensates With Internal Architecturementioning

confidence: 99%

Section: Examples Of Biomolecular Condensates With Internal Architecturementioning

confidence: 99%

Higher-order organization of biomolecular condensates

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Phase separation as principle implicated in the formation of biomolecular condensates has been discussed for a wide range of organisms [ 13 ] including bacteria [ 14 ], yeast [ 15 ], plants [ 16 ], animals [ 17 ], and also for viruses [ 18 ]. Example condensates include nucleoli [ 19 – 24 ], Cajal bodies [ 25 – 27 ], histone locus bodies [ 28 ], nuclear speckles and paraspeckles [ 29 – 34 ], PML nuclear bodies and APBs [ 35 – 38 ], SAM68 nuclear bodies [ 39 ], chromatin domains [ 40 – 51 ], transcription condensates [ 52 – 64 ], centromeres [ 65 – 67 ], DNA replication and repair condensates [ 68 – 79 ], stress granules and P-granules [ 80 – 82 ], and virus particles [ 83 – 92 ]. Several of these reside in the cell nucleus [ 93 ] and have genome-related functions ( Table 1 ).…”

Section: Condensate Formation By Phase Separationmentioning

confidence: 99%

Biomolecular condensates at sites of DNA damage: More than just a phase

Spegg

Altmeyer

2021

DNA Repair

View full text Add to dashboard Cite

Protein recruitment to DNA break sites is an integral part of the DNA damage response (DDR). Elucidation of the hierarchy and temporal order with which DNA damage sensors as well as repair and signaling factors assemble around chromosome breaks has painted a complex picture of tightly regulated macromolecular interactions that build specialized compartments to facilitate repair and maintenance of genome integrity. While many of the underlying interactions, e.g . between repair factors and damage-induced histone marks, can be explained by lock-and-key or induced fit binding models assuming fixed stoichiometries, structurally less well defined interactions, such as the highly dynamic multivalent interactions implicated in phase separation, also participate in the formation of multi-protein assemblies in response to genotoxic stress. Although much remains to be learned about these types of cooperative and highly dynamic interactions and their functional roles, the rapidly growing interest in material properties of biomolecular condensates and in concepts from polymer chemistry and soft matter physics to understand biological processes at different scales holds great promises. Here, we discuss nuclear condensates in the context of genome integrity maintenance, highlighting the cooperative potential between clustered stoichiometric binding and phase separation. Rather than viewing them as opposing scenarios, their combined effects can balance structural specificity with favorable physicochemical properties relevant for the regulation and function of multilayered nuclear condensates.

show abstract

“…Although some proteins that behave as transcriptional corepressors, such as the methyl-CpG binding protein 2 (MeCP2) and Nuclear receptor corepressor 2 (N-CoR2) (26,27), have been identi ed as components of nuclear speckles (26), their role in these nuclear bodies is unknown. To our knowledge, along with a recent report showing p53 cross-talking with nuclear speckles (28) this is one of the rst characterizations of a transcriptional regulator exerting a noncanonical function on the homeostasis of nuclear speckles.…”

Section: Discussionmentioning

confidence: 65%

Revealing RCOR2 as a regulatory component of nuclear speckles

Rivera

Verbel

Arancibia

et al. 2021

Preprint

View full text Add to dashboard Cite

Background Nuclear processes such as transcription and RNA maturation can be impacted by subnuclear compartmentalization in condensates and nuclear bodies. Here we characterize the nature of nuclear granules formed by REST corepressor 2 (RCOR2), a nuclear protein essential for pluripotency maintenance and central nervous system development. Results Using biochemical approaches and high-resolution microscopy, we reveal that RCOR2 is localized in nuclear speckles across multiple cell types, including neurons in the brain. RCOR2 forms complexes with nuclear speckle components such as SON, SRSF7, and SRRM2. When cells are exposed to chemical stress, RCOR2 behaves as a core component of the nuclear speckle and is stabilized by RNA. In turn, nuclear speckle morphology appears to depend on RCOR2. Specifically, RCOR2 knockdown results larger nuclear speckles, whereas overexpressing RCOR2 leads to smaller and rounder nuclear speckles. Conclusion Our study suggests that RCOR2 is a regulatory component of the nuclear speckle bodies, setting this co-repressor protein as a factor that controls nuclear speckles behavior.

show abstract

p53 mediates target gene association with nuclear speckles for amplified RNA expression

Cited by 61 publications

References 60 publications

Higher-order organization of biomolecular condensates

Higher-order organization of biomolecular condensates

Biomolecular condensates at sites of DNA damage: More than just a phase

Revealing RCOR2 as a regulatory component of nuclear speckles

Contact Info

Product

Resources

About