Proceedings of the National Academy of Sciences - PNAS, 2020-06, Vol.117 (25), p.14395-14404
2020
Details
- Autor(en) / Beteiligte
- Titel
- RIG-I regulates myeloid differentiation by promoting TRIM25-mediated ISGylation
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2020-06, Vol.117 (25), p.14395-14404
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- Electronic Journals Library
- Beschreibungen/Notizen
- Retinoic acid-inducible gene I (RIG-I) is up-regulated during granulocytic differentiation of acute promyelocytic leukemia (APL) cells induced by all-trans retinoic acid (ATRA). It has been reported that RIG-I recognizes virus-specific 5′-ppp-double-stranded RNA (dsRNA) and activates the type I interferons signaling pathways in innate immunity. However, the functions of RIG-I in hematopoiesis remain unclear, especially regarding its possible interaction with endogenous RNAs and the associated pathways that could contribute to the cellular differentiation and maturation. Herein, we identified a number of RIG-I–binding endogenous RNAs in APL cells following ATRA treatment, including the tripartite motif-containing protein 25 (TRIM25) messenger RNA (mRNA). TRIM25 encodes the protein known as an E3 ligase for ubiquitin/interferon (IFN)-induced 15-kDa protein (ISG15) that is involved in RIG-I–mediated antiviral signaling. We show that RIG-I could bind TRIM25 mRNA via its helicase domain and C-terminal regulatory domain, enhancing the stability of TRIM25 transcripts. RIG-I could increase the transcriptional expression of TRIM25 by caspase recruitment domain (CARD) domain through an IFN-stimulated response element. In addition, RIG-I activated other key genes in the ISGylation pathway by activating signal transducer and activator of transcription 1 (STAT1), including the modifier ISG15 and several enzymes responsible for the conjugation of ISG15 to protein substrates. RIG-I cooperated with STAT1/2 and interferon regulatory factor 1 (IRF1) to promote the activation of the ISGylation pathway. The integrity of ISGylation in ATRA or RIG-I–induced cell differentiation was essential given that knockdown of TRIM25 or ISG15 resulted in significant inhibition of this process. Our results provide insight into the role of the RIG-I-TRIM25-ISGylation axis in myeloid differentiation.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.1918596117Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7322067
- Format
- –
- Schlagworte
- Acute promyeloid leukemia, Biological Sciences, Caspase, Cell Differentiation, Cell Line, Tumor, Conjugation, Cytokines - genetics, Cytokines - metabolism, DEAD Box Protein 58 - metabolism, Differentiation (biology), DNA helicase, Domains, Double-stranded RNA, Gene Knockdown Techniques, Granulocytes - physiology, HEK293 Cells, Hematopoiesis, Humans, Innate immunity, Interferon, Interferon regulatory factor, Interferon regulatory factor 1, Leukemia, Promyeloid leukemia, Proteins, Receptors, Immunologic, Retinoic acid, Ribonucleic acid, RNA, RNA Stability, RNA viruses, RNA, Messenger - metabolism, Signal transduction, Signaling, Stat1 protein, Substrates, Transcription, Transcription Factors - genetics, Transcription Factors - metabolism, Tripartite Motif Proteins - genetics, Tripartite Motif Proteins - metabolism, Ubiquitin, Ubiquitin-protein ligase, Ubiquitin-Protein Ligases - genetics, Ubiquitin-Protein Ligases - metabolism, Ubiquitins - genetics, Ubiquitins - metabolism, Up-Regulation, Viruses