Drosha regulates gene expression independently of RNA cleavage function

Natalia Gromak; Martin Dienstbier; Sara Macias; Mireya Plass; Eduardo Eyras; Javier F. Cáceres; Nicholas J. Proudfoot

doi:10.1016/j.celrep.2013.11.032

Drosha regulates gene expression independently of RNA cleavage function

Natalia Gromak, Martin Dienstbier, Sara Macias, Mireya Plass, Eduardo Eyras, Javier F. Cáceres, Nicholas J. Proudfoot

Computational and RNA Biology

46 Citations (Scopus)

981 Downloads (Pure)

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.

Original language	English
Journal	Cell Reports
Volume	5
Issue number	6
Pages (from-to)	1499-510
Number of pages	12
DOIs	https://doi.org/10.1016/j.celrep.2013.11.032
Publication status	Published - 26 Dec 2013

Access to Document

10.1016/j.celrep.2013.11.032

Drosha Regulates Gene Expression Independently of RNA Cleavage FunctionFinal published version, 1.72 MB

Cite this

@article{63cfb8ad7f044d768df2872ab4992dc2,

title = "Drosha regulates gene expression independently of RNA cleavage function",

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.",

author = "Natalia Gromak and Martin Dienstbier and Sara Macias and Mireya Plass and Eduardo Eyras and C{\'a}ceres, {Javier F.} and Proudfoot, {Nicholas J.}",

year = "2013",

month = dec,

day = "26",

doi = "10.1016/j.celrep.2013.11.032",

language = "English",

volume = "5",

pages = "1499--510",

journal = "Cell Reports",

issn = "2639-1856",

publisher = "Cell Press",

number = "6",

}

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.

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 -

Drosha regulates gene expression independently of RNA cleavage function

Abstract

Access to Document

Fingerprint

Cite this