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

Valentina Fajner, Fabio Giavazzi, Simona Sala, Amanda Oldani, Emanuele Martini, Francesco Napoletano, Dario Parazzoli, Giuliana Cesare, Roberto Cerbino, Elena Maspero (), Thomas Vaccari () and Simona Polo ()
Additional contact information
Valentina Fajner: IFOM, Fondazione Istituto FIRC di Oncologia Molecolare
Fabio Giavazzi: Università degli Studi di Milano
Simona Sala: IFOM, Fondazione Istituto FIRC di Oncologia Molecolare
Amanda Oldani: IFOM, Fondazione Istituto FIRC di Oncologia Molecolare
Emanuele Martini: IFOM, Fondazione Istituto FIRC di Oncologia Molecolare
Francesco Napoletano: Laboratorio Nazionale CIB
Dario Parazzoli: IFOM, Fondazione Istituto FIRC di Oncologia Molecolare
Giuliana Cesare: Università degli Studi di Milano
Roberto Cerbino: Università degli Studi di Milano
Elena Maspero: IFOM, Fondazione Istituto FIRC di Oncologia Molecolare
Thomas Vaccari: Università degli Studi di Milano
Simona Polo: IFOM, Fondazione Istituto FIRC di Oncologia Molecolare

Nature Communications, 2021, vol. 12, issue 1, 1-19

Abstract: Abstract Specialised ribonucleoprotein (RNP) granules are a hallmark of polarized cells, like neurons and germ cells. Among their main functions is the spatial and temporal modulation of the activity of specific mRNA transcripts that allow specification of primary embryonic axes. While RNPs composition and role are well established, their regulation is poorly defined. Here, we demonstrate that Hecw, a newly identified Drosophila ubiquitin ligase, is a key modulator of RNPs in oogenesis and neurons. Hecw depletion leads to the formation of enlarged granules that transition from a liquid to a gel-like state. Loss of Hecw activity results in defective oogenesis, premature aging and climbing defects associated with neuronal loss. At the molecular level, reduced ubiquitination of the Fmrp impairs its translational repressor activity, resulting in altered Orb expression in nurse cells and Profilin in neurons.

Date: 2021
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DOI: 10.1038/s41467-021-25809-8

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