Journal
EMBO JOURNAL
Volume 31, Issue 24, Pages 4502-4510Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2012.319
Keywords
ALS; chromatin immunoprecipitation; Drosha; FUS/TLS; microRNA
Categories
Funding
- HFSP fellowship
- Telethon [GGP07049]
- Parent Project Italia
- AIRC
- IIT 'SEED'
- FIRB
- PRIN
- BEMM
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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
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