1. Drosha regulates gene expression independently of RNA cleavage function.
- Author
-
Gromak N, Dienstbier M, Macias S, Plass M, Eyras E, Cáceres JF, and Proudfoot NJ
- Subjects
- Binding Sites, HeLa Cells, Humans, Nuclear Cap-Binding Protein Complex metabolism, Promoter Regions, Genetic, Protein Binding, RNA Polymerase II metabolism, Ribonuclease III chemistry, Ribonuclease III genetics, MicroRNAs metabolism, RNA Processing, Post-Transcriptional, RNA Stability, Ribonuclease III metabolism, Transcription Elongation, Genetic
- 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., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF