The human DiGeorge syndrome critical region gene 8 and its D. melanogaster homolog are required for miRNA biogenesis

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Abstract

MicroRNAs (miRNAs) represent a family of small noncoding RNAs that are found in plants and animals (for recent reviews, see [1-5]). miRNAs are expressed in a developmentally and tissue-specific manner and regulate the translational efficiency and stability of partial or fully sequence- complementary mRNAs. miRNAs are excised in a stepwise process from double-stranded RNA precursors that are embedded in long RNA polymerase II primary transcripts (pri-miRNA) [6-10]. Drosha RNase III catalyzes the first excision event, the release in the nucleus [11-13] of a hairpin RNA (pre-miRNA), which is followed by export of the pre-miRNA to the cytoplasm [14-16] and further processing by Dicer to mature miRNAs [17-22]. Here, we characterize the human DGCR8, the DiGeorge syndrome critical region gene 8, and its Drosophila melanogaster homolog. We provide biochemical and cell-based readouts to demonstrate the requirement of DGCR8 for the maturation of miRNA primary transcripts. RNAi knockdown experiments of fly and human DGCR8 resulted in accumulation of pri-miRNAs and reduction of pre-miRNAs and mature miRNAs. Our results suggest that DGCR8 and Drosha interact in human cells and reside in a functional pri-miRNA processing complex.

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Landthaler, M., Yalcin, A., & Tuschl, T. (2004). The human DiGeorge syndrome critical region gene 8 and its D. melanogaster homolog are required for miRNA biogenesis. Current Biology, 14(23), 2162–2167. https://doi.org/10.1016/j.cub.2004.11.001

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