ArticleChemistry & biology2015
Cobalt(III) Protoporphyrin Activates the DGCR8 Protein and Can Compensate microRNA Processing Deficiency.
Article in Chemistry & biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 14 citations in OpenAlex.
- Cryo-EM structure of cadmium-bound human ABCB6.Communications biology · 2024Article
- Understanding the Variability of 22q11.2 Deletion Syndrome: The Role of Epigenetic Factors.Genes · 2024Review
- Characterization of a Cobalt-Substituted Globin-Coupled Oxygen Sensor Histidine Kinase fromACS omega · 2021Article
- Review
- Long-term impact of maternal high-fat diet on offspring cardiac health: role of micro-RNA biogenesis.Cell death discovery · 2019Article
- The Genetics and Epigenetics of 22q11.2 Deletion Syndrome.Frontiers in genetics · 2019Review
- CO and NO bind to Fe(II) DiGeorge critical region 8 heme but do not restore primary microRNA processing activity.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2016Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
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 Drosha RNase, both essential for processing canonical pri-miRNAs. To identify an agent that can compensate reduced DGCR8 expression, we screened for metalloporphyrins that can mimic the natural DGCR8 heme cofactor. We found that Co(III) protoporphyrin IX (PPIX) stably binds DGCR8 and activates it for pri-miRNA processing in vitro and in HeLa cells. Importantly, treating cultured Dgcr8(+/-) mouse neurons with Co(III)PPIX can compensate the pri-miRNA processing defects. Co(III)PPIX is effective at concentrations as low as 0.2 μM and is not degraded by heme degradation enzymes, making it useful as a research tool and a potential therapeutic.
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