The molecular language of membraneless organelles

Gomes, Edward; Shorter, James

doi:10.1074/jbc.tm118.001192

Cited by 629 publications

(635 citation statements)

References 172 publications

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“…These dynamic structures are condensates of macromolecules that are reversibly assembled in a process termed liquid–liquid phase separation. In recent years, phase separation has gain interest as a novel principle of cellular organization and regulation . The resulting assemblies concentrate certain molecules while excluding others, and hence, can speed up or slow down biochemical reactions and contribute to compartmentalize the biological processes taking place within the living cell.…”

Section: Reversible Oxidation Of Methionine and The Regulation Of Liqmentioning

confidence: 99%

“…In recent years, phase separation has gain interest as a novel principle of cellular organization and regulation. 41 F I G U R E 5 Methionine-mediated redox regulation of IκBα turnover. In the absence of stimuli, the NF-κB, formed by the proteins RelA and p50, is retained in the cytoplasm by the inhibitory protein IκB, with which forms a ternary complex.…”

Section: Reversible Oxidation Of Methionine and The Regulation Of Lmentioning

confidence: 99%

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Methionine in proteins: The Cinderella of the proteinogenic amino acids

Aledo

2019

Protein Science

104

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Methionine in proteins, apart from its role in the initiation of translation, is assumed to play a simple structural role in the hydrophobic core, in a similar way to other hydrophobic amino acids such as leucine, isoleucine, and valine. However, research from a number of laboratories supports the concept that methionine serves as an important cellular antioxidant, stabilizes the structure of proteins, participates in the sequence‐independent recognition of protein surfaces, and can act as a regulatory switch through reversible oxidation and reduction. Despite all these evidences, the role of methionine in protein structure and function is largely overlooked by most biochemists. Thus, the main aim of the current article is not so much to carry out an exhaustive review of the many and diverse processes in which methionine residues are involved, but to review some illustrative examples that may help the nonspecialized reader to form a richer and more precise insight regarding the role‐played by methionine residues in such processes.

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Section: Reversible Oxidation Of Methionine and The Regulation Of Liqmentioning

confidence: 99%

Section: Reversible Oxidation Of Methionine and The Regulation Of Lmentioning

confidence: 99%

Methionine in proteins: The Cinderella of the proteinogenic amino acids

Aledo

2019

Protein Science

104

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“…[42][43][44][45][46] Many key intracellular processes, including biomolecular localization, signaling, structuring of cytoplasm, as well as the protection of active components in cells rely on these organelles. [47][48][49][50][51][52][53][54] These intracellular structures have sparked growing research interests not only for their significant performances, but more importantly, for the scenario that they are assembled and compartmentalized through liquid-liquid phase separation (LLPS) which occurred spontaneously at mild conditions. [55][56][57] All of these discoveries about the intracellular structures can be used as important guidelines and design principles for developing cell-inspired biomaterials, which would show great potentials in a broad range of biomedical applications, such as delivery of drugs and vaccine for therapeutic purposes, [58,59] smart sensors for biomedical imaging and disease diagnosis, [60,61] soft robotics with stimuliresponsive and environmentally adaptive performances, [62,63] as well as force-bearing and wound healing scaffolds for tissue engineering.…”

Section: Introductionmentioning

confidence: 99%

Cell‐Inspired All‐Aqueous Microfluidics: From Intracellular Liquid–Liquid Phase Separation toward Advanced Biomaterials

et al. 2020

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Living cells have evolved over billions of years to develop structural and functional complexity with numerous intracellular compartments that are formed due to liquid–liquid phase separation (LLPS). Discovery of the amazing and vital roles of cells in life has sparked tremendous efforts to investigate and replicate the intracellular LLPS. Among them, all‐aqueous emulsions are a minimalistic liquid model that recapitulates the structural and functional features of membraneless organelles and protocells. Here, an emerging all‐aqueous microfluidic technology derived from micrometer‐scaled manipulation of LLPS is presented; the technology enables the state‐of‐art design of advanced biomaterials with exquisite structural proficiency and diversified biological functions. Moreover, a variety of emerging biomedical applications, including encapsulation and delivery of bioactive gradients, fabrication of artificial membraneless organelles, as well as printing and assembly of predesigned cell patterns and living tissues, are inspired by their cellular counterparts. Finally, the challenges and perspectives for further advancing the cell‐inspired all‐aqueous microfluidics toward a more powerful and versatile platform are discussed, particularly regarding new opportunities in multidisciplinary fundamental research and biomedical applications.

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“…Similar properties have been observed for EBOV inclusion bodies [10], suggesting that inclusion bodies of NSVs might generally represent liquid organelles. Such liquid organelles consist in most cases of RNA and RNA-binding proteins, and are formed by liquid-liquid phase separation, with multivalent low affinity interactions and intrinsically disordered protein regions being important drivers of their formation (reviewed in [53,54]). RNAs are important constituents of these liquid organelles and sometimes even the seed for their formation; however, in the case of mRNAs they have to be exported in order to reach ribosomes for translation.…”

Section: A Model For the Function Of Nxf1 In The Ebov Life Cyclementioning

confidence: 99%

The Ebola Virus Nucleoprotein Recruits the Nuclear RNA Export Factor NXF1 into Inclusion Bodies to Facilitate Viral Protein Expression

Wendt

Brandt

Bodmer

et al. 2020

Cells

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Ebola virus (EBOV) causes severe outbreaks of viral hemorrhagic fever in humans. While virus-host interactions are promising targets for antivirals, there is only limited knowledge regarding the interactions of EBOV with cellular host factors. Recently, we performed a genome-wide siRNA screen that identified the nuclear RNA export factor 1 (NXF1) as an important host factor for the EBOV life cycle. NXF1 is a major component of the nuclear mRNA export pathway that is usurped by many viruses whose life cycles include nuclear stages. However, the role of NXF1 in the life cycle of EBOV, a virus replicating in cytoplasmic inclusion bodies, remains unknown. In order to better understand the role of NXF1 in the EBOV life cycle, we performed a combination of co-immunoprecipitation and double immunofluorescence assays to characterize the interactions of NXF1 with viral proteins and RNAs. Additionally, using siRNA-mediated knockdown of NXF1 together with functional assays, we analyzed the role of NXF1 in individual aspects of the virus life cycle. With this approach we identified the EBOV nucleoprotein (NP) as a viral interaction partner of NXF1. Further studies revealed that NP interacts with the RNA-binding domain of NXF1 and competes with RNA for this interaction. Co-localization studies showed that RNA binding-deficient, but not wildtype NXF1, accumulates in NP-derived inclusion bodies, and knockdown experiments demonstrated that NXF1 is necessary for viral protein expression, but not for viral RNA synthesis. Finally, our results showed that NXF1 interacts with viral mRNAs, but not with viral genomic RNAs. Based on these results we suggest a model whereby NXF1 is recruited into inclusion bodies to promote the export of viral mRNA:NXF1 complexes from these sites. This would represent a novel function for NXF1 in the life cycle of cytoplasmically replicating viruses, and may provide a basis for new therapeutic approaches against EBOV, and possibly other emerging viruses.

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The molecular language of membraneless organelles

Cited by 629 publications

References 172 publications

Methionine in proteins: The Cinderella of the proteinogenic amino acids

Methionine in proteins: The Cinderella of the proteinogenic amino acids

Cell‐Inspired All‐Aqueous Microfluidics: From Intracellular Liquid–Liquid Phase Separation toward Advanced Biomaterials

The Ebola Virus Nucleoprotein Recruits the Nuclear RNA Export Factor NXF1 into Inclusion Bodies to Facilitate Viral Protein Expression

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