ArticleProceedings of the National Academy of Sciences of the United States of America2014
Processing of microRNA primary transcripts requires heme in mammalian cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
45 citing papers in PubMed, 88 citations in OpenAlex.
- Disrupting the circTNC/miR-582-5p/MAPK8 axis alleviates oxidative stress-induced trophoblast dysfunction in preeclampsia.Journal of molecular histology · 2026Article
- HOTTIP suppresses ferroptosis via mediating DGCR8/miR‑214‑3p/GPX4 regulatory axis in osteosarcoma.Oncology reports · 2025Article
- Interdependence of Pasha and Drosha for localization and function of the Microprocessor in C. elegans.Nature communications · 2025Article
- Article
- The structural landscape of Microprocessor-mediated processing of pri-let-7 miRNAs.Molecular cell · 2024Article
- A transcription-independent role for HIF-1α in modulating microprocessor assembly.Nucleic acids research · 2024Article
- Update on heme biosynthesis, tissue-specific regulation, heme transport, relation to iron metabolism and cellular energy.Liver international : official journal of the International Association for the Study of the Liver · 2024Review
- The structural landscape of Microprocessor mediated pri-bioRxiv : the preprint server for biology · 2024Article
- Regulation of Microprocessor assembly and localization via Pasha's WW domain inbioRxiv : the preprint server for biology · 2024Article
- Regulatory role of RNA-binding proteins in microRNA biogenesis.Frontiers in molecular biosciences · 2024Review
- Gas-sensing riboceptors.RNA biology · 2024Article
- Notes from the Underground: Heme Homeostasis inBiomolecules · 2023Review
- Article
- Modulation of Nrf2/HO-1 by Natural Compounds in Lung Cancer.Antioxidants (Basel, Switzerland) · 2023Review
- Depletion assisted hemin affinity (DAsHA) proteomics reveals an expanded landscape of heme-binding proteins in the human proteome.Metallomics : integrated biometal science · 2023Article
- Iron: Not Just a Passive Bystander in AITD.Nutrients · 2022Review
- Carbon Monoxide Signaling: Examining Its Engagement with Various Molecular Targets in the Context of Binding Affinity, Concentration, and Biologic Response.Pharmacological reviews · 2022Review
- Regulation of protein function and degradation by heme, heme responsive motifs, and CO.Critical reviews in biochemistry and molecular biology · 2022Review
- A vicious circle in breast cancer: The interplay between inflammation, reactive oxygen species, and microRNAs.Frontiers in oncology · 2022Review
- Modulation of MicroRNA Processing by Dicer via Its Associated dsRNA Binding Proteins.Non-coding RNA · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
DiGeorge syndrome critical region gene 8 (DGCR8) is the RNA-binding partner protein of the nuclease Drosha. DGCR8 and Drosha recognize and cleave primary transcripts of microRNAs (pri-miRNAs) in the maturation of canonical microRNAs (miRNAs) in animals. We previously reported that human, frog, and starfish DGCR8 bind heme when expressed in Escherichia coli and that Fe(III) heme activates apoDGCR8 in reconstituted pri-miRNA processing assays. However, the physiological relevance of heme in miRNA maturation has not been clear. Here, we present a live-cell pri-miRNA processing assay that produces robust signals and faithfully indicates DGCR8 and Drosha activities. We demonstrate that all known heme-binding-deficient DGCR8 mutants are defective in pri-miRNA processing in HeLa cells. DGCR8 contains a previously uncharacterized heme-binding motif, "IPCL," that is also required for its activity. Heme availability and biosynthesis in HeLa cells positively affect pri-miRNA processing and production of mature miRNA. These results establish an essential function for heme in pri-miRNA processing in mammalian cells. Our study suggests that abnormal heme biosynthesis and degradation may contribute to diseases via miRNA-mediated gene regulation networks.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.