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.

Hecw controls oogenesis and neuronal homeostasis by promoting the liquid state of ribonucleoprotein particles / V. Fajner, F. Giavazzi, S. Sala, A. Oldani, E. Martini, F. Napoletano, D. Parazzoli, G. Cesare, R. Cerbino, E. Maspero, T. Vaccari, S. Polo. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 12:1(2021), pp. 5488.1-5488.19. [10.1038/s41467-021-25809-8]

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

V. Fajner
Primo
;
F. Giavazzi
Secondo
;
S. Sala;F. Napoletano;G. Cesare;R. Cerbino;E. Maspero
;
T. Vaccari
Penultimo
;
S. Polo
Ultimo
2021

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.
Animals; Cytoplasmic Granules; Drosophila Proteins; Drosophila melanogaster; Embryo, Nonmammalian; Fragile X Mental Retardation Protein; Homeostasis; Longevity; Neurogenesis; Neurons; Oocytes; Oogenesis; Phase Transition; Profilins; Protein Biosynthesis; Protein Processing, Post-Translational; RNA-Binding Proteins; Ribonucleoproteins; Ubiquitin-Protein Ligases; Ubiquitination; Gene Expression Regulation, Developmental
Settore BIO/13 - Biologia Applicata
Settore MED/04 - Patologia Generale
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/878737
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