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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.

Original publication

DOI

10.1016/j.celrep.2013.11.032

Type

Journal article

Journal

Cell Rep

Publication Date

26/12/2013

Volume

5

Pages

1499 - 1510

Keywords

Binding Sites, HeLa Cells, Humans, MicroRNAs, Nuclear Cap-Binding Protein Complex, Promoter Regions, Genetic, Protein Binding, RNA Polymerase II, RNA Processing, Post-Transcriptional, RNA Stability, Ribonuclease III, Transcription Elongation, Genetic