The UBAP2L ortholog PQN-59 contributes to stress granule assembly and development in<i>C. elegans</i>

Abbatemarco, Simona; Bondaz, Alexandra; Schwager, Françoise; Wang, Jing; Hammell, Christopher M.; Gotta, Monica

doi:10.1101/2021.04.16.440123

Cited by 2 publications

(1 citation statement)

References 42 publications

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“…In agreement with these findings, we found that a 20 min shift from 20°C to 30°C was sufficient to increase the intensity of Nup foci in growing oocytes by Appendix Fig S4A and D) and significantly increase Nup condensation in embryos (Fig 4B). In contrast, the same conditions of oocyte arrest and mild heat stress did not change the distribution of the stress granule protein G3BP, which requires exposure to higher temperatures to condense (Abbatemarco et al, 2021;Fig 4A). Together these observations indicate that Nup foci assembly is readily enhanced by mild stress conditions.…”

Section: Nup Foci Assembly Is Enhanced By Oocyte Arrest Heat Stress A...mentioning

confidence: 93%

Nucleoporin foci are stress‐sensitive condensates dispensable for C. elegans nuclear pore assembly

et al. 2023

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Nucleoporins (Nups) assemble nuclear pores that form the permeability barrier between nucleoplasm and cytoplasm. Nucleoporins also localize in cytoplasmic foci proposed to function as pore preassembly intermediates. Here, we characterize the composition and incidence of cytoplasmic Nup foci in an intact animal, C. elegans. We find that, in young non-stressed animals, Nup foci only appear in developing sperm, oocytes and embryos, tissues that express high levels of nucleoporins. The foci are condensates of highly cohesive FG repeat-containing nucleoporins (FG-Nups), which are maintained near their solubility limit in the cytoplasm by posttranslational modifications and chaperone activity. Only a minor fraction of FG-Nup molecules concentrate in Nup foci, which dissolve during M phase and are dispensable for nuclear pore assembly. Nucleoporin condensation is enhanced by stress and advancing age, and overexpression of a single FG-Nup in postmitotic neurons is sufficient to induce ectopic condensation and organismal paralysis. We speculate that Nup foci are non-essential and potentially toxic condensates whose assembly is actively suppressed in healthy cells.

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Section: Nup Foci Assembly Is Enhanced By Oocyte Arrest Heat Stress A...mentioning

confidence: 93%

Nucleoporin foci are stress‐sensitive condensates dispensable for C. elegans nuclear pore assembly

et al. 2023

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PQN-59 antagonizes microRNA-mediated repression and functions in stress granule formation during C. elegans development

Hammell

Carlston

Weinmann

et al. 2021

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microRNAs (miRNAs) are potent regulators of gene expression that function in a variety of developmental and physiological processes by dampening the expression of their target genes at a post-transcriptional level. In many gene regulatory networks (GRNs), miRNAs function in a switch-like manner whereby their expression and activity elicit a transition from one stable pattern of gene expression to a distinct, equally stable pattern required to define a nascent cell fate. While the importance of miRNAs that function in this capacity are clear, we have less of an understanding of the cellular factors and mechanisms that ensure the robustness of this form of regulatory bistability. In a screen to identify suppressors of temporal patterning phenotypes that result from ineffective miRNA-mediated target repression during C. elegans development, we identified pqn-59, an ortholog of human UBAP2L, as a novel factor that antagonizes the activities of multiple heterochronic miRNAs. Specifically, we find that depletion of pqn-59 can restore normal development in animals with reduced miRNA activity. Importantly, inactivation of pqn-59 is not sufficient to bypass the requirement of these regulatory RNAs within the heterochronic GRN. The pqn-59 gene encodes an abundant, cytoplasmically localized and unstructured protein that harbors three essential “prion-like” domains. These domains exhibit LLPS properties in vitro and normally function to limit PQN-59 diffusion in the cytoplasm in vivo . Like human UBAP2L, PQN-59’s localization becomes highly dynamic during stress conditions where it re-distributes to cytoplasmic stress granules and is important for their formation. Proteomic analysis of PQN-59 complexes from embryonic extracts indicates that PQN-59 and human UBAP2L interact with orthologous cellular components involved in RNA metabolism and promoting protein translation and that PQN-59 additionally interacts with proteins involved in transcription and intracellular transport. Finally, we demonstrate that pqn-59 depletion results in the stabilization of several mature miRNAs (including those involved in temporal patterning) without altering steady-state pre-miRNAs levels indicating that PQN-59 may ensure the bistability of some GRNs that require miRNA functions by promoting miRNA turnover and, like UBAP2L, enhancing protein translation.

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The UBAP2L ortholog PQN-59 contributes to stress granule assembly and development inC. elegans

Cited by 2 publications

References 42 publications

Nucleoporin foci are stress‐sensitive condensates dispensable for C. elegans nuclear pore assembly

Nucleoporin foci are stress‐sensitive condensates dispensable for C. elegans nuclear pore assembly

PQN-59 antagonizes microRNA-mediated repression and functions in stress granule formation during C. elegans development

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