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- Title
Drosha controls dendritic cell development by cleaving messenger RNAs encoding inhibitors of myelopoiesis.
- Authors
Johanson, Timothy M; Keown, Ashleigh A; Cmero, Marek; Yeo, Janet H C; Kumar, Amit; Lew, Andrew M; Zhan, Yifan; Chong, Mark M W
- 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.
- Subjects
DENDRITIC cells; MESSENGER RNA; RIBONUCLEASE III; HEMATOPOIETIC stem cells; PROGENITOR cells
- Publication
Nature Immunology, 2015, Vol 16, Issue 11, p1134
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.3293