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

被引:17
作者
D'Ambra, Eleonora [1 ,2 ]
Santini, Tiziana [1 ,2 ]
Vitiello, Erika [1 ]
D'Uva, Sara [1 ]
Silenzi, Valentina [1 ,2 ]
Morlando, Mariangela [4 ]
Bozzoni, Irene [1 ,2 ,3 ]
机构
[1] Sapienza Univ Rome, Dept Biol & Biotechnol Charles Darwin, Rome, Italy
[2] Fdn Ist Italiano Tecnol, Ctr Life Nano & Neurosci, Rome, Italy
[3] Ist Italiano Tecnol, Ctr Human Technol, Genoa, Italy
[4] Univ Perugia, Dept Pharmaceut Sci, Dept Excellence 2018 2022, Perugia, Italy
基金
欧盟地平线“2020”;
关键词
IN-SITU HYBRIDIZATION; CIRCULAR RNAS; AXONAL-TRANSPORT; EMERGING ROLES; MUTATIONS; PROTEINS; FUS/TLS; BIOGENESIS; GRANULES; ABUNDANT;
D O I
10.1016/j.isci.2021.103504
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
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页数:22
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