TDP-43 (TAR DNA-binding protein 43) is an RNA-binding protein implicated in RNA metabolism at several levels. Even if ubiquitously expressed, it is considered as a neuronal activity-responsive factor and a major signature for neurological pathologies, making the comprehension of its activity in the nervous system a very challenging issue. TDP-43 has also been described as an accessory component of the Drosha-DGCR8 (DiGeorge syndrome critical region gene 8) microprocessor complex, which is crucially involved in basal and tissue-specific RNA processing events. In the present study, we exploited in vitro neuronal differentiation systems to investigate the TDP-43 demand for the microprocessor function, focusing on both its canonical microRNA biosynthetic activity and its alternative role as a post-transcriptional regulator of gene expression. Our findings reveal a novel role for TDP-43 as an essential factor that controls the stability of Drosha protein during neuronal differentiation, thus globally affecting the production of microRNAs. We also demonstrate that TDP-43 is required for the Drosha-mediated regulation of Neurogenin 2, a master gene orchestrating neurogenesis, whereas post-transcriptional control of Dgcr8, another Drosha target, resulted to be TDP-43-independent. These results implicate a previously uncovered contribution of TDP-43 in regulating the abundance and the substrate specificity of the microprocessor complex and provide new insights into TDP-43 as a key player in neuronal differentiation. © 2013 Springer Science+Business Media New York.

TDP-43 regulates the microprocessor complex activity during in vitro neuronal differentiation / DI CARLO, Valerio; Elena, Grossi; Pietro, Laneve; Morlando, Mariangela; DINI MODIGLIANI, Stefano; Ballarino, Monica; Bozzoni, Irene; Caffarelli, Elisa. - In: MOLECULAR NEUROBIOLOGY. - ISSN 0893-7648. - ELETTRONICO. - 48:3(2013), pp. 952-963. [10.1007/s12035-013-8564-x]

TDP-43 regulates the microprocessor complex activity during in vitro neuronal differentiation

DI CARLO, VALERIO;MORLANDO, MARIANGELA;DINI MODIGLIANI, STEFANO;BALLARINO, MONICA;BOZZONI, Irene;CAFFARELLI, ELISA
2013

Abstract

TDP-43 (TAR DNA-binding protein 43) is an RNA-binding protein implicated in RNA metabolism at several levels. Even if ubiquitously expressed, it is considered as a neuronal activity-responsive factor and a major signature for neurological pathologies, making the comprehension of its activity in the nervous system a very challenging issue. TDP-43 has also been described as an accessory component of the Drosha-DGCR8 (DiGeorge syndrome critical region gene 8) microprocessor complex, which is crucially involved in basal and tissue-specific RNA processing events. In the present study, we exploited in vitro neuronal differentiation systems to investigate the TDP-43 demand for the microprocessor function, focusing on both its canonical microRNA biosynthetic activity and its alternative role as a post-transcriptional regulator of gene expression. Our findings reveal a novel role for TDP-43 as an essential factor that controls the stability of Drosha protein during neuronal differentiation, thus globally affecting the production of microRNAs. We also demonstrate that TDP-43 is required for the Drosha-mediated regulation of Neurogenin 2, a master gene orchestrating neurogenesis, whereas post-transcriptional control of Dgcr8, another Drosha target, resulted to be TDP-43-independent. These results implicate a previously uncovered contribution of TDP-43 in regulating the abundance and the substrate specificity of the microprocessor complex and provide new insights into TDP-43 as a key player in neuronal differentiation. © 2013 Springer Science+Business Media New York.
2013
neurogenin 2; microprocessor; neuronal differentiation; mirnas; drosha
01 Pubblicazione su rivista::01a Articolo in rivista
TDP-43 regulates the microprocessor complex activity during in vitro neuronal differentiation / DI CARLO, Valerio; Elena, Grossi; Pietro, Laneve; Morlando, Mariangela; DINI MODIGLIANI, Stefano; Ballarino, Monica; Bozzoni, Irene; Caffarelli, Elisa. - In: MOLECULAR NEUROBIOLOGY. - ISSN 0893-7648. - ELETTRONICO. - 48:3(2013), pp. 952-963. [10.1007/s12035-013-8564-x]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/540538
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