Journal article

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

Timothy M Johanson, Ashleigh A Keown, Marek Cmero, Janet HC Yeo, Amit Kumar, Andrew M Lew, Yifan Zhan, Mark MW Chong

Nature Immunology | NATURE PUBLISHING GROUP | Published : 2015

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 n..

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Grants

Awarded by National Health and Medical Research Council, Australia


Awarded by Juvenile Diabetes Research Foundation


Awarded by Diabetes Australia Research Trust


Funding Acknowledgements

We thank C. Yates for animal husbandry. Supported by the National Health and Medical Research Council, Australia (637338, 1004541, 1042211 and 1079586 to M.M.W.C.; 1037321, 1043414 and 1080321 to A.M.L.), the Juvenile Diabetes Research Foundation (5-2011-100 to M.M.W.C.), the Diabetes Australia Research Trust (Y13G-CHOM to M.M.W.C.), the Australian Research Council (M.M.W.C.) and the Victorian State Government Operational Infrastructure Support and Australian National Health and Medical Research Council Research Institute Infrastructure Support Scheme.