Format

Send to

Choose Destination
EMBO J. 2012 Dec 12;31(24):4502-10. doi: 10.1038/emboj.2012.319.

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

Author information

1
Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, Rome, Italy.

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.

PMID:
23232809
PMCID:
PMC3545295
DOI:
10.1038/emboj.2012.319
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center