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Cell Rep. 2013 Dec 26;5(6):1499-510. doi: 10.1016/j.celrep.2013.11.032. Epub 2013 Dec 19.

Drosha regulates gene expression independently of RNA cleavage function.

Author information

1
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. Electronic address: natalia.gromak@path.ox.ac.uk.
2
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
3
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.
4
Computational Genomics Group, Universitat Pompeu Fabra, Dr. Aiguader 88, 08003 Barcelona, Spain; The Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark.
5
Computational Genomics Group, Universitat Pompeu Fabra, Dr. Aiguader 88, 08003 Barcelona, Spain; Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluís Companys 23, 08010 Barcelona, Spain.
6
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. Electronic address: nicholas.proudfoot@path.ox.ac.uk.

Erratum in

  • Cell Rep. 2014 Jun 12;7(5):1753-4.

Abstract

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 promoter-proximal 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.

PMID:
24360955
PMCID:
PMC3898267
DOI:
10.1016/j.celrep.2013.11.032
[Indexed for MEDLINE]
Free PMC Article
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