Drosha regulates gene expression independently of RNA cleavage function

Gromak, Natalia; Dienstbier, Martin; Macias, Sara; Plass Pórtulas, Mireya, 1982-; Eyras Jiménez, Eduardo; Cáceres, Javier F.; Proudfoot, Nicholas J.

doi:http://dx.doi.org/10.1016/j.celrep.2013.11.032

Drosha regulates gene expression independently of RNA cleavage function

License

Citation

Gromak N, Dienstbier M, Macias S, Plass M, Eyras E, Caceres JF, Proudfoot NJ. Drosha regulates gene expression independently of RNA cleavage function. Cell Reports. 2013;5(6):1499-510. DOI: 10.1016/j.celrep.2013.11.032

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.