Drosha regulates gene expression independently of RNA cleavage function

TY - JOUR

T1 - Drosha regulates gene expression independently of RNA cleavage function

AU - Gromak, Natalia

AU - Dienstbier, Martin

AU - Macias, Sara

AU - Plass, Mireya

AU - Eyras, Eduardo

AU - Cáceres, Javier F.

AU - Proudfoot, Nicholas J.

N1 - Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2013/12/26

Y1 - 2013/12/26

N2 - 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.

AB - 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.

U2 - 10.1016/j.celrep.2013.11.032

DO - 10.1016/j.celrep.2013.11.032

M3 - Journal article

C2 - 24360955

SN - 2639-1856

VL - 5

SP - 1499

EP - 1510

JO - Cell Reports

JF - Cell Reports

IS - 6

ER -