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

Mariangela Morlando (1) , Stefano Dini Modigliani (1) , Giulia Torrelli (1) , Alessandro Rosa (1) , Valerio Di Carlo (1) , Elisa Caffarelli (2, 3) , Irene Bozzoni (1, 3, 2, 4)

1 Department of Biology and Biotechnology "Charles Darwin"
2 CNR | IBPM - CNR Istituto di Biologia e Patologia Molecolari [Roma]
3 Center for Life Nano Science at Sapienza
4 Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti

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.

Domaines: Biologie moléculaire

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, 2012, 31 (24), pp.4502-10. ⟨10.1038/emboj.2012.319⟩. ⟨pasteur-00955859⟩