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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, ISSN 1530-6860,
DOI: 10.1096/fj.202002108R,
[Article]

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.

Item Type: Article
Erschienen: 2020
Creators: 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
Title: Modulation of microRNA processing by 5-lipoxygenase.
Language: English
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.

Journal or Publication Title: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Divisions: 10 Department of Biology
10 Department of Biology > Synthetic Genetic Circuits
Date Deposited: 24 Nov 2020 07:21
DOI: 10.1096/fj.202002108R
Identification Number: pmid:33205517
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