Cobalt(III) Protoporphyrin Activates the DGCR8 Protein and Can Compensate microRNA Processing Deficiency

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Cobalt(III) Protoporphyrin Activates the DGCR8 Protein and Can Compensate microRNA Processing Deficiency.

Processing of microRNA primary transcripts (pri-miRNAs) is highly regulated and defects in the processing machinery play a key role in many human diseases. In 22q11.2 deletion syndrome (22q11.2DS), heterozygous deletion of DiGeorge critical region gene 8 (DGCR8) causes a processing deficiency, which contributes to abnormal brain development. The DGCR8 protein is the RNA-binding partner of Drosh...

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Ferric, not ferrous, heme activates RNA-binding protein DGCR8 for primary microRNA processing.

The RNA-binding protein DiGeorge Critical Region 8 (DGCR8) and its partner nuclease Drosha are essential for processing of microRNA (miRNA) primary transcripts (pri-miRNAs) in animals. Previous work showed that DGCR8 forms a highly stable and active complex with ferric [Fe(III)] heme using two endogenous cysteines as axial ligands. Here we report that reduction of the heme iron to the ferrous [...

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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...

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ژورنال

عنوان ژورنال: Chemistry & Biology

سال: 2015

ISSN: 1074-5521

DOI: 10.1016/j.chembiol.2015.05.015