期刊
CELL REPORTS
卷 5, 期 6, 页码 1499-1510出版社
CELL PRESS
DOI: 10.1016/j.celrep.2013.11.032
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资金
- Medical Research Council
- Wellcome Trust [095518/Z/11/Z]
- Spanish Ministry of Science
- Sandra Ibarra Foundation [BIO2008-01091, BIO2011-23920, CSD2009-00080]
- Novo Nordisk Foundation
- Royal Society University Research fellowship
- MRC NIRG [MR/J007870/1]
- Wellcome Trust [095518/Z/11/Z] Funding Source: Wellcome Trust
- MRC [MR/J007870/1, MC_PC_U127584479] Funding Source: UKRI
- Ataxia UK [7126] Funding Source: researchfish
- Medical Research Council [MC_PC_U127584479, MR/J007870/1] Funding Source: researchfish
- Motor Neurone Disease Association [Gromak/Jun11/6278] Funding Source: researchfish
- ICREA Funding Source: Custom
Drosha is the main RNase III-like enzyme involved in the process of microRNA (miRNA) biogenesis in the nucleus. Using whole-genome ChIP-on-chip analysis, we demonstrate that, in addition to miRNA sequences, Drosha specifically binds promoterproximal regions of many human genes in a transcription-dependent manner. This binding is not associated with miRNA production or RNA cleavage. Drosha knockdown in HeLa cells downregulated nascent gene transcription, resulting in a reduction of polyadenylated mRNA produced from these gene regions. Furthermore, we show that this function of Drosha is dependent on its N-terminal protein-interaction domain, which associates with the RNA-binding protein CBP80 and RNA Polymerase II. Consequently, we uncover a previously unsuspected RNA cleavage-independent function of Drosha in the regulation of human gene expression.
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