CircRNAs belong to a family of RNA molecules which are conserved in evolution, have tissue-specific expression, and are abundant in neuronal cells. Here, we define several features of circ-Hdgfrp3 and describe interesting alterations occurring in motor neurons (MNs) carrying ALS-associated FUS mutations. Through a highly sensitive in situ approach we describe that circ-Hdgfrp3 traffics along neurites, while upon oxidative stress it is retained in the perinuclear region. While in wild-type stressed MNs, circ-Hdgfrp3 localizes in stress granules (SGs), in MNs carrying mutant FUS, a higher proportion of circ-Hdgfrp3 was trapped into cytoplasmic aggregates. Upon stress removal, circ-Hdgfrp3 was easily freed from SGs whereas it was less efficiently released from FUS-aggregates. We found that the human circ-Hdgfrp3 counterpart was also similarly associated to mutant FUS-aggregates in stressed neuronal cells. Overall, the alteration of circ-Hdgfrp3 trafficking adds a further layer of complexity to the role of FUS-aggregates in ALS disease.

Circ-Hdgfrp3 shuttles along neurites and is trapped in aggregates formed by ALS-associated mutant FUS / D'Ambra, Eleonora; Santini, Tiziana; Vitiello, Erika; D'Uva, Sara; Silenzi, Valentina; Morlando, Mariangela; Bozzoni, Irene. - In: ISCIENCE. - ISSN 2589-0042. - 24:12(2021). [10.1016/j.isci.2021.103504]

Circ-Hdgfrp3 shuttles along neurites and is trapped in aggregates formed by ALS-associated mutant FUS

D'Ambra, Eleonora
Primo
;
Santini, Tiziana;Vitiello, Erika;D'Uva, Sara;Silenzi, Valentina;Morlando, Mariangela
;
Bozzoni, Irene
2021

Abstract

CircRNAs belong to a family of RNA molecules which are conserved in evolution, have tissue-specific expression, and are abundant in neuronal cells. Here, we define several features of circ-Hdgfrp3 and describe interesting alterations occurring in motor neurons (MNs) carrying ALS-associated FUS mutations. Through a highly sensitive in situ approach we describe that circ-Hdgfrp3 traffics along neurites, while upon oxidative stress it is retained in the perinuclear region. While in wild-type stressed MNs, circ-Hdgfrp3 localizes in stress granules (SGs), in MNs carrying mutant FUS, a higher proportion of circ-Hdgfrp3 was trapped into cytoplasmic aggregates. Upon stress removal, circ-Hdgfrp3 was easily freed from SGs whereas it was less efficiently released from FUS-aggregates. We found that the human circ-Hdgfrp3 counterpart was also similarly associated to mutant FUS-aggregates in stressed neuronal cells. Overall, the alteration of circ-Hdgfrp3 trafficking adds a further layer of complexity to the role of FUS-aggregates in ALS disease.
2021
biological sciences; cellular neuroscience; molecular neuroscience
01 Pubblicazione su rivista::01a Articolo in rivista
Circ-Hdgfrp3 shuttles along neurites and is trapped in aggregates formed by ALS-associated mutant FUS / D'Ambra, Eleonora; Santini, Tiziana; Vitiello, Erika; D'Uva, Sara; Silenzi, Valentina; Morlando, Mariangela; Bozzoni, Irene. - In: ISCIENCE. - ISSN 2589-0042. - 24:12(2021). [10.1016/j.isci.2021.103504]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1622370
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