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FUS stimulates microRNA biogenesis by facilitating co-transcriptional Drosha recruitment.

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.
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Submitted on : Wednesday, March 5, 2014 - 2:25:09 PM
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Mariangela Morlando, Stefano Dini Modigliani, Giulia Torrelli, Alessandro Rosa, Valerio Di Carlo, et al.. FUS stimulates microRNA biogenesis by facilitating co-transcriptional Drosha recruitment.. EMBO Journal, EMBO Press, 2012, 31 (24), pp.4502-10. ⟨10.1038/emboj.2012.319⟩. ⟨pasteur-00955859⟩



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