Gromak, NataliaDienstbier, MartinMacias, SaraPlass Pórtulas, Mireya, 1982-Eyras Jiménez, EduardoCáceres, Javier F.Proudfoot, Nicholas J.2015-06-042015-06-042013Gromak 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.2013.11.0322211-1247http://hdl.handle.net/10230/23725Drosha 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.application/pdfeng© 2013, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 International http://creativecommons.org/licenses/by-nc-nd/3.0/ http://dx.doi.org/10.1016/j.celrep.2013.11.032RNA-polimerasesGenètica molecularinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.celrep.2013.11.032info:eu-repo/semantics/openAccess