microRNA abundance has been shown to depend on the amount of the microprocessor components or, in some cases, on specific auxiliary co-factors. In this paper, we show that the FUS/TLS (fused in sarcoma/translocated in liposarcoma) protein, associated with familial forms of Amyotrophic Lateral Sclerosis (ALS), contributes to the biogenesis of a specific subset of microRNAs. Among them, species with roles in neuronal function, differentiation and synaptogenesis were identified. We also show that FUS/TLS is recruited to chromatin at sites of their transcription and binds the corresponding pri-microRNAs. Moreover, FUS/TLS depletion leads to decreased Drosha level at the same chromatin loci. Limited FUS/TLS depletion leads to a reduced microRNA biogenesis and we suggest a possible link between FUS mutations affecting nuclear/cytoplasmic partitioning of the protein and altered neuronal microRNA biogenesis in ALS pathogenesis. The EMBO Journal (2012) 31, 4502-4510. doi:10.1038/emboj.2012.319

FUS stimulates microRNA biogenesis by facilitating co-transcriptional Drosha recruitment / Morlando, Mariangela; DINI MODIGLIANI, Stefano; Torrelli, Giulia; Rosa, Alessandro; DI CARLO, Valerio; Caffarelli, Elisa; Bozzoni, Irene. - In: EMBO JOURNAL. - ISSN 0261-4189. - STAMPA. - 31:24(2012), pp. 4502-4510. [10.1038/emboj.2012.319]

FUS stimulates microRNA biogenesis by facilitating co-transcriptional Drosha recruitment

MORLANDO, MARIANGELA;DINI MODIGLIANI, STEFANO;TORRELLI, GIULIA;ROSA, ALESSANDRO;DI CARLO, VALERIO;CAFFARELLI, ELISA;BOZZONI, Irene
2012

Abstract

microRNA abundance has been shown to depend on the amount of the microprocessor components or, in some cases, on specific auxiliary co-factors. In this paper, we show that the FUS/TLS (fused in sarcoma/translocated in liposarcoma) protein, associated with familial forms of Amyotrophic Lateral Sclerosis (ALS), contributes to the biogenesis of a specific subset of microRNAs. Among them, species with roles in neuronal function, differentiation and synaptogenesis were identified. We also show that FUS/TLS is recruited to chromatin at sites of their transcription and binds the corresponding pri-microRNAs. Moreover, FUS/TLS depletion leads to decreased Drosha level at the same chromatin loci. Limited FUS/TLS depletion leads to a reduced microRNA biogenesis and we suggest a possible link between FUS mutations affecting nuclear/cytoplasmic partitioning of the protein and altered neuronal microRNA biogenesis in ALS pathogenesis. The EMBO Journal (2012) 31, 4502-4510. doi:10.1038/emboj.2012.319
2012
als; chromatin immunoprecipitation; drosha; fus/tls; microrna
01 Pubblicazione su rivista::01a Articolo in rivista
FUS stimulates microRNA biogenesis by facilitating co-transcriptional Drosha recruitment / Morlando, Mariangela; DINI MODIGLIANI, Stefano; Torrelli, Giulia; Rosa, Alessandro; DI CARLO, Valerio; Caffarelli, Elisa; Bozzoni, Irene. - In: EMBO JOURNAL. - ISSN 0261-4189. - STAMPA. - 31:24(2012), pp. 4502-4510. [10.1038/emboj.2012.319]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/506075
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