Hecw controls oogenesis and neuronal homeostasis by promoting the liquid state of ribonucleoprotein particles

Fajner, Valentina; Giavazzi, Fabio; Sala, Simona; Oldani, Amanda; Martini, Emanuele; Napoletano, Francesco; Parazzoli, Dario; Cesare, Giuliana; Cerbino, Roberto; Maspero, Elena; Vaccari, Thomas; Polo, Simona

doi:10.1038/s41467-021-25809-8

Cited by 8 publications

(7 citation statements)

References 86 publications

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“…Moreover, the properties and functions of RNA-binding proteins can be disrupted upon phase transitions. For example, in Drosophila egg chambers in the absence of the E3 ubiquitin ligase HECW, the Me31B RNA-binding protein transitions from small granules in a liquid phase to larger granules in a gel-like phase, and translational repression of target mRNAs is deregulated ( Fajner et al 2021 ). Since slower dynamics and increased stability can occur as RNP granules increase in size, we asked if imaging-associated stress affects phase transitions of four RNA-binding proteins that condense into large RNP granules in meiotically arrested oocytes of fog-2 females.…”

Section: Resultsmentioning

confidence: 99%

Imaging-associated stress causes divergent phase transitions of RNA-binding proteins in the Caenorhabditis elegans germ line

Elaswad

Munderloh

Watkins

et al. 2022

G3 Genes|Genomes|Genetics

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One emerging paradigm of cellular organization of RNA and RNA binding proteins is the formation of membraneless organelles (MLOs). Examples of MLOs include several types of ribonucleoprotein granules that form via phase separation. A variety of intracellular pH changes and post-translational modifications, as well as extracellular stresses can stimulate the condensation of proteins into granules. For example, the assembly of stress granules induced by oxidative stress, osmotic stress, and heat stress has been well-characterized in a variety of somatic cell types. In the germ line, similar stress-induced condensation of proteins occurs; however, less is known about the role of phase separation during gamete production. Researchers who study phase transitions often make use of fluorescent reporters to study the dynamics of RNA binding proteins during live-cell imaging. In this report, we demonstrate that common conditions of live-imaging C. elegans can cause an inadvertent stress and trigger phase transitions of RNA binding proteins. We show this imaging-associated stress stimulates decondensation of multiple germ granule proteins, and condensation of several P-body proteins. Proteins within larger RNP granules in meiotically-arrested oocytes do not appear to be as sensitive to the stress as proteins in diakinesis oocytes of young hermaphrodites, with the exception of the germ granule protein PGL-1. Our results have important methodological implications for all researchers using live-cell imaging techniques. The data also suggest that the RNA binding proteins within large RNP granules of arrested oocytes may have distinct phases which we characterize in our companion paper.

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Section: Resultsmentioning

confidence: 99%

Imaging-associated stress causes divergent phase transitions of RNA-binding proteins in the Caenorhabditis elegans germ line

Elaswad

Munderloh

Watkins

et al. 2022

G3 Genes|Genomes|Genetics

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show abstract

“…Moreover, the properties and functions of RNA binding proteins can be disrupted upon phase transitions. For example, in Drosophila egg chambers in the absence of the E3 ubiquitin ligase HECW, the Me31B RNA binding protein transitions from small granules in a liquid phase to larger granules in a gel-like phase, and translational repression of target mRNAs is deregulated (Fajner et al 2021). Since slower dynamics and increased stability can occur as RNP granules increase in size, we asked if imaging stress affects phase transitions of four RNA binding proteins that condense into large RNP granules in meiotically arrested oocytes of fog-2 females.…”

Section: Imaging Stress Causes Divergent Phase Transitions Of Rna Bin...mentioning

confidence: 99%

Imaging-induced stress causes divergent phase transitions of RNA binding proteins in the C. elegans germ line

Watkins

Elaswad

Pestrue

et al. 2021

Preprint

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One emerging paradigm of cellular organization of RNA and RNA binding proteins is the formation of membraneless organelles (MLOs). Examples of MLOs include several types of RNP (ribonucleoprotein) granules that form via phase separation. Proper regulation of the phase transitions of RNA binding proteins is critical as dysregulation can lead to disease states. Germ granules are small RNP granules conserved across metazoa. In C. elegans, when oogenesis undergoes an extended meiotic arrest, germ granules assemble into much larger, more complex RNP granules whose hypothesized function is to regulate RNA metabolism and maintain oocyte quality. As a step towards gaining insight into the function of RNP granules, in this report we characterize distinct phases for four RNA binding proteins in arrested oocytes. We find that PGL-1 is dynamic and has liquid-like properties, while MEG-3 has gel-like properties, both similar to their properties in small germ granules of embryos. We also show that MEX-3 exhibits gel-like properties in many regards but is more dynamic than MEG-3. We find CGH-1 is dynamic but does not consistently behave liquid-like, and may be an intermediate phase within RNP granules. We also show that the distinct phases of the RNA binding proteins are associated with differential responses to stress.

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“…In recent years, the potential of DDM to study transport phenomena in complex media has been explored in different directions. Notable examples include the microrheological characterization of viscoelastic fluids [28][29][30] and the investigation of anomalous transport and relaxation dynamics of crowded biopolymeric networks both in vivo [31,32] and in vitro [33][34][35].…”

Section: Introductionmentioning

confidence: 99%

“…We also build on an approach originally proposed in Refs. [5,32] to study intracellular and intercellular motility, which we extend here to extract the MSD and the non-Gaussian parameter directly from the experimentally determined ISFs. Finally, we propose a simple model to elucidate the nontrivial connection between selfdiffusion of tracer particles-typically probed in real space-and the collective relaxation of the associated density fluctuations, as probed by the ConDDM reciprocal space analysis.…”

Section: Introductionmentioning

confidence: 99%

Reciprocal Space Study of Brownian Yet Non-Gaussian Diffusion of Small Tracers in a Hard-Sphere Glass

et al. 2022

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The simultaneous presence of normal (Brownian) diffusion and non-Gaussian statistics of particle displacements has been identified as a recurring motif for a broad spectrum of physical and biological systems. While not yet fully understood, it is generally accepted that a key ingredient for observing this Brownian yet non-Gaussian (BNG) diffusion is that the environment hosting the particles appears stationary and homogenous on the small length and time scales, while displaying significant fluctuations on larger distances and/or longer time scales. To date, most of the experimental studies on systems displaying BNG diffusion have been performed in direct space, usually via a combination of optical microscopy and particle tracking to quantify the particle’s self-diffusion. Here, we demonstrate that a reciprocal space analysis of the density fluctuations caused by the particle motion as a function of the wave vector enables the investigation of BNG diffusion in situations where single-particle tracking is impossible. To accomplish this aim, we use confocal differential dynamic microscopy (ConDDM) to study the BNG dynamics of diluted sub-resolution tracers diffusing in a glassy matrix of larger hard spheres. We first elucidate the nontrivial connection between the tracer self-diffusion and collective relaxation of the resulting density fluctuations. We find that the experimentally determined intermediate scattering functions are in excellent agreement with the recent predictions of a “diffusing diffusivity” model of BNG diffusion, whose analytical predictions are available only in reciprocal space. Our results show that studying BNG diffusion in reciprocal space can be an invaluable strategy to access the fast, anomalous dynamics occurring at very small scales in crowded environments.

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Hecw controls oogenesis and neuronal homeostasis by promoting the liquid state of ribonucleoprotein particles

Cited by 8 publications

References 86 publications

Imaging-associated stress causes divergent phase transitions of RNA-binding proteins in the Caenorhabditis elegans germ line

Imaging-associated stress causes divergent phase transitions of RNA-binding proteins in the Caenorhabditis elegans germ line

Imaging-induced stress causes divergent phase transitions of RNA binding proteins in the C. elegans germ line

Reciprocal Space Study of Brownian Yet Non-Gaussian Diffusion of Small Tracers in a Hard-Sphere Glass

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