Multivalent interactions with RNA drive recruitment and dynamics in biomolecular condensates in Xenopus oocytes

Cabral, Sarah E; Otis, Jessica P.; Mowry, Kimberly L.

doi:10.1016/j.isci.2022.104811

Cited by 9 publications

(14 citation statements)

References 59 publications

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“…These interactions can include specific interactions with RNA-binding proteins or nonspecific interactions with charged intrinsically disordered proteins (IDPs). While many phase separation studies have focused on IDPs and the necessity of key proteins in RNP granules, the significance of RNA in BMCs is increasingly being recognized. − Recent work has shown that RNA can not only drive phase separation but also play a role in condensate viscoelasticity and gelation, − morphology, ,− organization, − and client partitioning ,, through a variety of interaction-based mechanisms. These include the inhibition and induction of conformational changes in protein binding partners, the formation of Watson–Crick interactions in repeat sequences, electrostatic interactions with polycation partners, ,,, and potential structure-induced effects. ,, …”

Section: Introductionmentioning

confidence: 99%

Short PolyA RNA Homopolymers Undergo Mg²⁺-Mediated Kinetically Arrested Condensation

2022

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RNA−RNA interactions have increasingly been recognized for their potential to shape the mesoscale properties of biomolecular condensates, influencing morphology, organization, and material state through networking interactions. While most studies have focused on networking via Watson−Crick base pairing interactions, previous work has suggested a potential for noncanonical RNA−RNA interactions to also give rise to condensation and alter overall material state. Here, we test the phase separation of short polyA RNA (polyrA) homopolymers. We discover and characterize the potential for short polyrA sequences to form RNA condensates at lower Mg 2+ concentrations than previously observed, which appear as internally arrested droplets with slow polyrA diffusion despite continued fusion. Our work also reveals a negative cooperativity effect between the effects of Mg 2+ and Na + on polyrA condensation. Finally, we observe that polyrA sequences can act as promoters of phase separation in mixed sequences. These results demonstrate the potential for noncanonical interactions to act as networking stickers, leading to specific condensation properties inherent to polyrA composition and structure, with implications for the fundamental physical chemistry of the system and function of polyA RNA in biology.

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Section: Introductionmentioning

confidence: 99%

Short PolyA RNA Homopolymers Undergo Mg²⁺-Mediated Kinetically Arrested Condensation

2022

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“…Long noncoding RNAs with unique secondary structures are thought to be especially important in the phase separation process by binding to RBPs (Somasundaram et al, 2022). For some condensates in vitro, RNA molecules, not proteins, are required form maintenance of condensates (Cabral et al, 2022). Introducing unstructured regions into mRNA molecules can also affect processes such as translation initiation, pointing also to the importance of RNA structure in such condensates (Lai et al, 2022).…”

Section: Multivalency and Intrinsically Disordered Proteinsmentioning

confidence: 99%

Molecular Grammar of RNA-binding Protein Interactions in Formation and Function of Ribonucleoprotein Complexes

Adamek¹

2023

Socratic Lectures 8

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Ribonucleoproteins (RNPs) are macromolecular assemblies of proteins along RNA molecules to carry out specialized cellular processes. Understanding how RNA binding proteins (RBPs) and RNA sequences determine the interactions to form RNPs and ultimately steer biomolecular processes remains poorly understood. There is a mounting evidence that RNP assembly de-pends on the formation of a network of transient, multivalent RBP RNA and RBP RBP interac-tions, particularly between tyrosine residues from intrinsically disordered domains and argi-nine residues from RNA-binding domains of RBPs. Furthermore, RBPs, especially their intrin-sically disordered regions, are hotspots for posttranslational modification (PTM) sites. Alt-hough PTMs have been well catalogued, little is known about how these modifications regulate RNP assembly and function. Some initial studies introduced the concept of the so-called phos-pho-switch, in which RBPs require phosphorylation for condensation of larger RNP complexes, but it remains unclear how this contributes to the protein function and the pattern of selective protein binding to RNA molecules. This short review will take a look at what is currently known in the field of RNPs, their interactions, and the phase-separated biomolecular conden-sates, which are intimately connected to RNPs and are important for several key cell processes. Keywords: Ribonucleoproteins; RNA binding proteins; Multivalency; Intrinsically disordered proteins; Posttranslational modifications

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“…Although proteins in L‐bodies exhibit liquid‐like properties with high dynamics, L‐bodies are not spherical like most liquid condensates. The irregular morphology of L‐bodies is likely conferred by a nondynamic RNA mesh‐ or scaffold‐like structure (Cabral et al, 2022; Neil et al, 2021). Liquid dynamics in nonspherical structures is a property L‐bodies share with the ER‐associated condensate, TIS granules.…”

Section: Mechanisms Of Rna Localizationmentioning

confidence: 99%

“…It has been speculated that RNA often acts as a scaffold in condensates that supports nonessential client molecules (reviewed in Hentze et al, 2018). Once formed, RNA can regulate the phase and material properties of condensates (Cabral et al, 2022; Elbaum‐Garfinkle et al, 2015; H. Zhang et al, 2015). The properties and signals governing condensate disassembly remain largely unknown, however in the nucleus relatively high concentrations of RNA can result in condensate re‐entrant phase behavior, with the dissolution of phase‐separated behavior of RBPs with prion‐like domains (P. R. Banerjee et al, 2017; Henninger et al, 2021; Maharana et al, 2018; Milin & Deniz, 2018).…”

Section: Functional Relevance Of Mrna Localizationmentioning

confidence: 99%

Hitting the mark: Localization of mRNA and biomolecular condensates in health and disease

Otis

Mowry

2023

WIREs RNA

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Subcellular mRNA localization is critical to a multitude of biological processes such as development of cellular polarity, embryogenesis, tissue differentiation, protein complex formation, cell migration, and rapid responses to environmental stimuli and synaptic depolarization. Our understanding of the mechanisms of mRNA localization must now be revised to include formation and trafficking of biomolecular condensates, as several biomolecular condensates that transport and localize mRNA have recently been discovered. Disruptions in mRNA localization can have catastrophic effects on developmental processes and biomolecular condensate biology and have been shown to contribute to diverse diseases. A fundamental understanding of mRNA localization is essential to understanding how aberrations in this biology contribute the etiology of numerous cancers though support of cancer cell migration and biomolecular condensate dysregulation, as well as many neurodegenerative diseases, through misregulation of mRNA localization and biomolecular condensate biology.This article is categorized under: RNA Export and Localization > RNA Localization RNA in Disease and Development > RNA in Disease RNA in Disease and Development > RNA in Development

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Multivalent interactions with RNA drive recruitment and dynamics in biomolecular condensates in Xenopus oocytes

Cited by 9 publications

References 59 publications

Short PolyA RNA Homopolymers Undergo Mg²⁺-Mediated Kinetically Arrested Condensation

Short PolyA RNA Homopolymers Undergo Mg²⁺-Mediated Kinetically Arrested Condensation

Molecular Grammar of RNA-binding Protein Interactions in Formation and Function of Ribonucleoprotein Complexes

Hitting the mark: Localization of mRNA and biomolecular condensates in health and disease

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Multivalent interactions with RNA drive recruitment and dynamics in biomolecular condensates in Xenopus oocytes

Cited by 9 publications

References 59 publications

Short PolyA RNA Homopolymers Undergo Mg2+-Mediated Kinetically Arrested Condensation

Short PolyA RNA Homopolymers Undergo Mg2+-Mediated Kinetically Arrested Condensation

Molecular Grammar of RNA-binding Protein Interactions in Formation and Function of Ribonucleoprotein Complexes

Hitting the mark: Localization of mRNA and biomolecular condensates in health and disease

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Short PolyA RNA Homopolymers Undergo Mg²⁺-Mediated Kinetically Arrested Condensation

Short PolyA RNA Homopolymers Undergo Mg²⁺-Mediated Kinetically Arrested Condensation