FUS stimulates microRNA biogenesis by facilitating co-transcriptional Drosha recruitment

被引：190

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：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

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

页码：4502 / 4510

页数：9

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