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FUS stimulates microRNA biogenesis by facilitating co‐transcriptional Drosha recruitment
Author(s) -
Morlando Mariangela,
Dini Modigliani Stefano,
Torrelli Giulia,
Rosa Alessandro,
Di Carlo Valerio,
Caffarelli Elisa,
Bozzoni Irene
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2012.319
Subject(s) - drosha , biology , microrna , biogenesis , ribonuclease iii , microbiology and biotechnology , genetics , computational biology , rna interference , gene , rna
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.