The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Department of Medical Biology, The University of Melbourne, Parkville, Australia.
Nat Immunol. 2015 Nov;16(11):1134-41. doi: 10.1038/ni.3293. Epub 2015 Oct 5.
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.
为了研究微 RNA（miRNA）途径是否对树突状细胞（DC）的发育至关重要，我们评估了阻断 Drosha 和 Dicer 的效果，这两种酶是 miRNA 生物发生的关键。我们发现，尽管 Dicer 的缺乏有一定的影响，但 Drosha 的缺乏完全阻止了 DC 的发育，更广泛地阻止了髓系细胞的发育。这表明虽然 miRNA 途径确实发挥了作用，但 Drosha 的非 miRNA 功能尤其关键。Drosha 抑制了早期造血祖细胞中两种编码髓系细胞抑制物的 mRNA 的表达。我们发现 Drosha 直接切割这些 mRNA 中的茎环结构，并且这种 mRNA 降解对于髓系细胞的发育是必需的。因此，我们已经确定了一种调节 DC 和其他髓样细胞发育的机制。
