FUS stimulates microRNA biogenesis by facilitating co-transcriptional Drosha recruitment

被引：183
作者：
Morlando, Mariangela [1 ]
Modigliani, Stefano Dini [1 ]
Torrelli, Giulia [1 ]
Rosa, Alessandro [1 ]
Di Carlo, Valerio [1 ]
Caffarelli, Elisa [2 ,3 ]
Bozzoni, Irene [1 ,2 ,3 ,4 ]
机构：
[1] Univ Roma La Sapienza, Dept Biol & Biotechnol Charles Darwin, I-00185 Rome, Italy
[2] Univ Roma La Sapienza, Ist Italiano Tecnol, Ctr Life Nano Sci Sapienza, I-00185 Rome, Italy
[3] Univ Roma La Sapienza, CNR, Inst Mol Biol & Pathol, I-00185 Rome, Italy
[4] Univ Roma La Sapienza, Fdn Cenci Bolognetti, Inst Pasteur, I-00185 Rome, Italy
来源：
EMBO JOURNAL | 2012年 / 31卷 / 24期
关键词：
ALS; chromatin immunoprecipitation; Drosha; FUS/TLS; microRNA; AMYOTROPHIC-LATERAL-SCLEROSIS; BINDING-PROTEIN; IN-VIVO; RNA; GENE; EXPRESSION; MUTATIONS; PROMOTER; TLS; NEURODEGENERATION;
D O I：
10.1038/emboj.2012.319
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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
引用
收藏
页码：4502 / 4510
页数：9
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