Drosha controls dendritic cell development by cleaving messenger RNAs encoding inhibitors of myelopoiesis

Timothy M Johanson; Ashleigh A Keown; Marek Cmero; Janet H C Yeo; Amit Kumar; Andrew M Lew; Yifan Zhan; Mark M W Chong

doi:10.1038/ni.3293

Drosha controls dendritic cell development by cleaving messenger RNAs encoding inhibitors of myelopoiesis

Nat Immunol. 2015 Nov;16(11):1134-41. doi: 10.1038/ni.3293. Epub 2015 Oct 5.

Authors

Timothy M Johanson^{1

2

3}, Ashleigh A Keown³, Marek Cmero³, Janet H C Yeo^{1

2

3}, Amit Kumar³, Andrew M Lew^{1

2

4}, Yifan Zhan^{1

2}, Mark M W Chong^{3

5}

Affiliations

¹ The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
² Department of Medical Biology, The University of Melbourne, Parkville, Australia.
³ St. Vincent's Institute of Medical Research, Fitzroy, Australia.
⁴ Department of Microbiology &Immunology, The University of Melbourne, Parkville, Australia.
⁵ Department of Medicine (St. Vincent's), The University of Melbourne, Fitzroy, Australia.

PMID: 26437240
DOI: 10.1038/ni.3293

Abstract

To investigate if the microRNA (miRNA) pathway is required for dendritic cell (DC) development, we assessed the effect of ablating Drosha and Dicer, the two enzymes central to miRNA biogenesis. We found that while Dicer deficiency had some effect, Drosha deficiency completely halted DC development and halted myelopoiesis more generally. This indicated that while the miRNA pathway did have a role, it was a non-miRNA function of Drosha that was particularly critical. Drosha repressed the expression of two mRNAs encoding inhibitors of myelopoiesis in early hematopoietic progenitors. We found that Drosha directly cleaved stem-loop structure within these mRNAs and that this mRNA degradation was necessary for myelopoiesis. We have therefore identified a mechanism that regulates the development of DCs and other myeloid cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Base Sequence
Cell Differentiation / genetics
Cell Differentiation / immunology
DEAD-box RNA Helicases / deficiency
DEAD-box RNA Helicases / genetics
DEAD-box RNA Helicases / immunology
Dendritic Cells / cytology
Dendritic Cells / immunology*
Dendritic Cells / metabolism*
Gene Expression Regulation, Developmental
Gene Knockdown Techniques
Hematopoietic Stem Cells / cytology
Hematopoietic Stem Cells / immunology
Hematopoietic Stem Cells / metabolism
Inflammation / immunology
Inflammation / pathology
Mice
Mice, Inbred C57BL
Mice, Knockout
MicroRNAs / genetics
MicroRNAs / metabolism
Molecular Sequence Data
Myelopoiesis / genetics
Myelopoiesis / immunology*
Myosin Light Chains / antagonists & inhibitors
Myosin Light Chains / genetics
Myosin Light Chains / metabolism
Nucleic Acid Conformation
RNA, Messenger / chemistry
RNA, Messenger / genetics
RNA, Messenger / metabolism*
Ribonuclease III / deficiency
Ribonuclease III / genetics
Ribonuclease III / immunology*

Substances

MicroRNAs
Myosin Light Chains
RNA, Messenger
Dicer1 protein, mouse
Drosha protein, mouse
Ribonuclease III
DEAD-box RNA Helicases

Associated data

GEO/GSE61305