Loss of ISWI Function in Drosophila Nuclear Bodies Drives Cytoplasmic Redistribution of Drosophila TDP-43

International Journal of Molecular Sciences

Giorgio Giurato¹  Fabian Feiguin²  Giulia Romano²  Lorenzo Li Greci³  Davide F. V. Corona³  Andrea Attardi³  Antonia Maria Rita Ingrassia³  Maria Cristina Onorati³  Luca Lo Piccolo³  Rosa Bonaccorso³  Martina Sollazzo³ 

[1] Genomix4Life srl, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi (SA), Italy;International Centre for Genetic Engineering and Biotechnology Padriciano 99, 34149 Trieste, Italy;STEBICEF, Viale delle Scienze, Edificio 16, Università degli Studi di Palermo, 90128 Palermo, Italy;

关键词: Drosophila;    nuclear body;    omega speckles;    dTDP-43;    hnRNPs;    omega speckles;    neurodegenerative diseases;    gene expression;    gene regulation;   

DOI  :  10.3390/ijms19041082

来源: DOAJ

【 摘 要 】

Over the past decade, evidence has identified a link between protein aggregation, RNA biology, and a subset of degenerative diseases. An important feature of these disorders is the cytoplasmic or nuclear aggregation of RNA-binding proteins (RBPs). Redistribution of RBPs, such as the human TAR DNA-binding 43 protein (TDP-43) from the nucleus to cytoplasmic inclusions is a pathological feature of several diseases. Indeed, sporadic and familial forms of amyotrophic lateral sclerosis (ALS) and fronto-temporal lobar degeneration share as hallmarks ubiquitin-positive inclusions. Recently, the wide spectrum of neurodegenerative diseases characterized by RBPs functions’ alteration and loss was collectively named proteinopathies. Here, we show that TBPH (TAR DNA-binding protein-43 homolog), the Drosophila ortholog of human TDP-43 TAR DNA-binding protein-43, interacts with the arcRNA hsrω and with hsrω-associated hnRNPs. Additionally, we found that the loss of the omega speckles remodeler ISWI (Imitation SWI) changes the TBPH sub-cellular localization to drive a TBPH cytoplasmic accumulation. Our results, hence, identify TBPH as a new component of omega speckles and highlight a role of chromatin remodelers in hnRNPs nuclear compartmentalization.

【 授权许可】

Unknown