GSK3 inhibitors CHIR99021 and 6-bromoindirubin-3'-oxime inhibit microRNA maturation in mouse embryonic stem cells

Scientific Reports
Yongyan WuYong Zhang

Abstract

Wnt/β-catenin signalling plays a prominent role in maintaining self-renewal and pluripotency of mouse embryonic stem cells (mESCs). microRNAs (miRNAs) have critical roles in maintaining pluripotency and directing reprogramming. To investigate the effect of GSK3 inhibitors on miRNA expression, we analysed the miRNA expression profile of J1 mESCs in the absence or presence of CHIR99021 (CHIR) or 6-bromoindirubin-3'-oxime (BIO) by small RNA deep-sequencing. The results demonstrate that CHIR and BIO decrease mature miRNAs of most miRNA species, 90.4% and 98.1% of the differentially expressed miRNAs in BIO and CHIR treated cells were downregulated respectively. CHIR and BIO treatment leads to a slight upregulation of the primary transcripts of the miR-302-367 cluster and miR-181 family of miRNAs, these miRNAs are activated by Wnt/β-catenin signalling. However, the precursor and mature form of the miR-302-367 cluster and miR-181 family of miRNAs are downregulated by CHIR, suggesting CHIR inhibits maturation of primary miRNA. Western blot analysis shows that BIO and CHIR treatment leads to a reduction of the RNase III enzyme Drosha in the nucleus. These data suggest that BIO and CHIR inhibit miRNA maturation by disturbing nuclear loca...Continue Reading

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Citations

Jun 27, 2018·Acta Biochimica Et Biophysica Sinica·Yingxiang LiuZekun Guo
Dec 3, 2016·Nucleic Acids Research·Claire E FletcherCharlotte L Bevan
Feb 11, 2020·Frontiers in Cell and Developmental Biology·Marta Silvia MagriJosé Luis Gómez-Skarmeta
Oct 14, 2020·Journal of Assisted Reproduction and Genetics·Marta Vila-CejudoElena Ibáñez
Mar 14, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Agnieszka GizakDariusz Rakus
Jul 25, 2017·Cell Chemical Biology·Marcus John LongYimon Aye

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Datasets Mentioned

BETA
GSE54145

Methods Mentioned

BETA
immunoprecipitation
Assay
PCR

Software Mentioned

Database for Annotation , Visualization , and Integrated Disco...
SAS

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