Drosha Regulates Gene Expression Independently of RNA Cleavage Function

作者：Gromak Natalia^*; Dienstbier Martin; Macias Sara; Plass Mireya; Eyras Eduardo; Caceres Javier F; Proudfoot Nicholas J

来源：Cell Reports, 2013, 5(6): 1499-1510.

DOI：10.1016/j.celrep.2013.11.032

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.

• 出版日期2013-12