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Modulation of microRNA processing by 5-lipoxygenase

Uebbing, Stella ; Kreiß, Marius ; Scholl, Friederike ; Häfner, Ann-Kathrin ; Sürün, Duran ; Garscha, Ulrike ; Werz, Oliver ; Basavarajappa, Devaraj ; Samuelsson, Bengt ; Rådmark, Olof ; Suess, Beatrix ; Steinhilber, Dieter (2020)
Modulation of microRNA processing by 5-lipoxygenase.
In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 35 (2)
doi: 10.1096/fj.202002108R
Artikel, Bibliographie

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Kurzbeschreibung (Abstract)

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.

Typ des Eintrags: Artikel
Erschienen: 2020
Autor(en): Uebbing, Stella ; Kreiß, Marius ; Scholl, Friederike ; Häfner, Ann-Kathrin ; Sürün, Duran ; Garscha, Ulrike ; Werz, Oliver ; Basavarajappa, Devaraj ; Samuelsson, Bengt ; Rådmark, Olof ; Suess, Beatrix ; Steinhilber, Dieter
Art des Eintrags: Bibliographie
Titel: Modulation of microRNA processing by 5-lipoxygenase
Sprache: Englisch
Publikationsjahr: 17 November 2020
Titel der Zeitschrift, Zeitung oder Schriftenreihe: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Jahrgang/Volume einer Zeitschrift: 35
(Heft-)Nummer: 2
DOI: 10.1096/fj.202002108R
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Kurzbeschreibung (Abstract):

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.

ID-Nummer: pmid:33205517
Zusätzliche Informationen:

Artikel-ID: e21193

Fachbereich(e)/-gebiet(e): 10 Fachbereich Biologie
10 Fachbereich Biologie > Synthetic RNA biology
Hinterlegungsdatum: 24 Nov 2020 07:21
Letzte Änderung: 08 Jan 2024 07:52
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