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Stress-dependent miR-980 regulation of Rbfox1/A2bp1 promotes ribonucleoprotein granule formation and cell survival

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  • Mariya M. Kucherenko

    (Max Planck Institute for Biophysical Chemistry)

  • Halyna R. Shcherbata

    (Max Planck Institute for Biophysical Chemistry)

Abstract

Upon stress, profound post-transcriptional adjustments of gene expression occur in spatially restricted, subcellular, membraneless compartments, or ribonucleoprotein (RNP) granules, which are formed by liquid phase separation of RNA-binding proteins with low complexity sequence domains (LCDs). Here, we show that Rbfox1 is an LCD-containing protein that aggregates into liquid droplets and amyloid-like fibers and promiscuously joins different nuclear and cytoplasmic RNP granules. Using Drosophila oogenesis as an in vivo system for stress response, we demonstrate a mechanism by which Rbfox1 promotes cell survival. The stress-dependent miRNA miR-980 acts to buffer Rbfox1 levels, since it targets only those Rbfox1 transcripts that contain extended 3′UTRs. Reduced miR-980 expression during stress leads to increased Rbfox1 levels, widespread formation of various RNP granules, and increased cell viability. We show that human RBFOX proteins also contain multiple LCDs and form membraneless compartments, suggesting that the RNP granule-linked control of cellular adaptive responses may contribute to a wide range of RBFOX-associated pathologies in humans.

Suggested Citation

  • Mariya M. Kucherenko & Halyna R. Shcherbata, 2018. "Stress-dependent miR-980 regulation of Rbfox1/A2bp1 promotes ribonucleoprotein granule formation and cell survival," Nature Communications, Nature, vol. 9(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02757-w
    DOI: 10.1038/s41467-017-02757-w
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    Cited by:

    1. Yu Chang & Chuandong Xie & Hong Liu & Shengli Huang & Pengfei Wang & Wenling Qin & Hailong Yan, 2022. "Organocatalytic atroposelective construction of axially chiral N, N- and N, S-1,2-azoles through novel ring formation approach," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Mariya M. Kucherenko & Pengchao Sang & Juquan Yao & Tara Gransar & Saphala Dhital & Jana Grune & Szandor Simmons & Laura Michalick & Dag Wulsten & Mario Thiele & Orr Shomroni & Felix Hennig & Ruhi Yet, 2023. "Elastin stabilization prevents impaired biomechanics in human pulmonary arteries and pulmonary hypertension in rats with left heart disease," Nature Communications, Nature, vol. 14(1), pages 1-23, December.

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