MicroRNA (miRNA) maturation is initiated by Microprocessor composed of RNase III DROSHA and its cofactor DGCR8, whose fidelity is critical for generation of functional miRNAs. To understand how Microprocessor recognizes pri-miRNAs, we here reconstitute human Microprocessor with purified recombinant proteins. We find that Microprocessor is an ∼364 kDa heterotrimeric complex of one DROSHA and two...

The ribonuclease III enzyme Drosha has a central role in the biogenesis of microRNA (miRNA) by binding and cleaving hairpin structures in primary RNA transcripts into precursor miRNAs (pre-miRNAs). Many miRNA genes are located within protein-coding host genes and cleaved by Drosha in a manner that is coincident with splicing of introns by the spliceosome. The close proximity of splicing and pre...

RNase III proteins play key roles in microRNA (miRNA) biogenesis. The nuclear RNase III Drosha cleaves primary miRNAs (pri-miRNAs) to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic RNase III Dicer to generate mature miRNAs. While Dicer (class III) and other simple RNase III proteins (class I) have been studied intensively, the class II enzyme Drosha remains to be...

The RNase III enzyme Drosha initiates microRNA (miRNA) biogenesis in the nucleus by cleaving primary miRNA transcripts into shorter precursor molecules that are subsequently exported into the cytoplasm for further processing. While numerous disease states appear to be associated with aberrant expression of Drosha, the molecular mechanisms that regulate its protein levels are largely unknown. He...

PURPOSE miRNAs can regulate the biological processes, including differentiation, proliferation and apoptosis. DICER and DROSHA are two members of RNase III family, playing pivotal roles in the pathway of miRNAs biogenesis. In this study, we hypothesized that genetic variations of the DICER and DROSHA genes were associated with the bladder cancer risk. EXPERIMENTAL DESIGN We performed a case-c...

DROSHA is a nuclear RNase III enzyme responsible for cleaving primary microRNAs (miRNAs) into precursor miRNAs and thus is essential for the biogenesis of canonical miRNAs. DICER is a cytoplasmic RNase III enzyme that not only cleaves precursor miRNAs to produce mature miRNAs but also dissects naturally formed/synthetic double-stranded RNAs to generate small interfering RNAs (siRNAs). To invest...

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by binding to the cellular transcript leading to translational repression or degradation of the target mRNA. Dicer and Drosha are the miRNA processing enzymes that are required for the maturation of miRNAs. Here, we investigated the role of Dicer and Drosha for angiogenesis. Endothelial cells were transfected with siRNA a...

Drosha is an RNA III-like enzyme that has an aberrant expression in some tumors. Our previous studies showed the aberrant Drosha in gastric tumors. However, the roles of nuclear Drosha, the main regulator of microRNA (miRNA) biogenesis, in gastric cancer (GC) progression remain poorly understood. In this study, we demonstrated that nuclear Drosha is significantly associated with cell invasion o...

Adult neural stem cells (NSCs) are defined by their inherent capacity to self-renew and give rise to neurons, astrocytes, and oligodendrocytes. In vivo, however, hippocampal NSCs do not generate oligodendrocytes for reasons that have remained enigmatic. Here, we report that deletion of Drosha in adult dentate gyrus NSCs activates oligodendrogenesis and reduces neurogenesis at the expense of gli...

A critical step during human microRNA maturation is the processing of the primary microRNA transcript by the nuclear RNaseIII enzyme Drosha to generate the approximately 60-nucleotide precursor microRNA hairpin. How Drosha recognizes primary RNA substrates and selects its cleavage sites has remained a mystery, especially given that the known targets for Drosha processing show no discernable seq...