Stella Uebbing, Marius Kreiß, Friederike Scholl, Ann-Kathrin Häfner, Duran Sürün, Ulrike Garscha, Oliver Werz, Devaraj Basavarajappa, Bengt Samuelsson, Olof Rådmark, Beatrix Süß, Dieter Steinhilber
- The miRNA biogenesis is tightly regulated to avoid dysfunction and consequent disease development. Here, we describe modulation of miRNA processing as a novel noncanonical function of the 5-lipoxygenase (5-LO) enzyme in monocytic cells. In differentiated Mono Mac 6 (MM6) cells, we found an in situ interaction of 5-LO with Dicer, a key enzyme in miRNA biogenesis. RNA sequencing of small noncoding RNAs revealed a functional impact, knockout of 5-LO altered the expression profile of several miRNAs. Effects of 5-LO could be observed at two levels. qPCR analyses thus indicated that (a) 5-LO promotes the transcription of the evolutionarily conserved miR-99b/let-7e/miR-125a cluster and (b) the 5-LO-Dicer interaction downregulates the processing of pre-let-7e, resulting in an increase in miR-125a and miR-99b levels by 5-LO without concomitant changes in let-7e levels in differentiated MM6 cells. Our observations suggest that 5-LO regulates the miRNA profile by modulating the Dicer-mediated processing of distinct pre-miRNAs. 5-LO inhibits the formation of let-7e which is a well-known inducer of cell differentiation, but promotes the generation of miR-99b and miR-125a known to induce cell proliferation and the maintenance of leukemic stem cell functions.
MetadatenVerfasserangaben: | Stella Uebbing, Marius Kreiß, Friederike Scholl, Ann-Kathrin HäfnerORCiDGND, Duran Sürün, Ulrike Garscha, Oliver WerzORCiDGND, Devaraj Basavarajappa, Bengt Samuelsson, Olof RådmarkORCiD, Beatrix SüßGND, Dieter SteinhilberORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-565102 |
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DOI: | https://doi.org/10.1096/fj.202002108R |
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ISSN: | 1530-6860 |
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ISSN: | 0892-6638 |
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Pubmed-Id: | https://pubmed.ncbi.nlm.nih.gov/33205517 |
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Titel des übergeordneten Werkes (Deutsch): | The FASEB journal |
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Verlag: | Wiley |
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Verlagsort: | Hoboken, NJ |
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Dokumentart: | Wissenschaftlicher Artikel |
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Sprache: | Englisch |
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Datum der Veröffentlichung (online): | 17.11.2020 |
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Datum der Erstveröffentlichung: | 17.11.2020 |
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Veröffentlichende Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Datum der Freischaltung: | 19.11.2020 |
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Freies Schlagwort / Tag: | 5-lipoxygenase; Dicer; cancer; inflammation; leukotriene; miRNA |
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Jahrgang: | 2020 |
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Seitenzahl: | 15 |
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HeBIS-PPN: | 476115043 |
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Institute: | Biochemie, Chemie und Pharmazie / Biochemie und Chemie |
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DDC-Klassifikation: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
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| 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
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Sammlungen: | Universitätspublikationen |
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Lizenz (Englisch): | Creative Commons - Namensnennung-Nicht kommerziell 4.0 |
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