Embryonic MicroRNA-369 controls metabolic splicing factors and urges cellular reprograming

Masamitsu Konno, Jun Koseki, Koichi Kawamoto, Naohiro Nishida, Hidetoshi Matsui, Dyah Laksmi Dewi, Miyuki Ozaki, Yuko Noguchi, Koshi Mimori, Noriko Gotoh, Nobuhiro Tanuma, Hiroshi Shima, Yuichiro Doki, Masaki Mori, Hideshi Ishii

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Noncoding microRNAs inhibit translation and lower the transcript stability of coding mRNA, however miR-369 s, in aberrant silencing genomic regions, stabilizes target proteins under cellular stress. We found that in vitro differentiation of embryonic stem cells led to chromatin methylation of histone H3K4 at the miR-369 region on chromosome 12qF in mice, which is expressed in embryonic cells and is critical for pluripotency. Proteomic analyses revealed that miR-369 stabilized translation of pyruvate kinase (Pkm2) splicing factors such as HNRNPA2B1. Overexpression of miR-369 stimulated Pkm2 splicing and enhanced induction of cellular reprogramming by induced pluripotent stem cell factors, whereas miR-369 knockdown resulted in suppression. Furthermore, immunoprecipitation analysis showed that the Argonaute complex contained the fragile X mental retardation-related protein 1 and HNRNPA2B1 in a miR-369-depedent manner. Our findings demonstrate a unique role of the embryonic miR-369-HNRNPA2B1 axis in controlling metabolic enzyme function, and suggest a novel pathway linking epigenetic, transcriptional, and metabolic control in cell reprogramming.

Original languageEnglish
Article numbere0132789
JournalPLoS One
Volume10
Issue number7
DOIs
Publication statusPublished - Jul 15 2015

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MicroRNAs
microRNA
translation (genetics)
Fragile X Mental Retardation Protein
stem cell factor
Induced Pluripotent Stem Cells
pyruvate kinase
Stem Cell Factor
Pyruvate Kinase
Methylation
embryonic stem cells
RNA Stability
Embryonic Stem Cells
Chromosomes
Stem cells
Immunoprecipitation
Epigenomics
histones
epigenetics
methylation

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Konno, M., Koseki, J., Kawamoto, K., Nishida, N., Matsui, H., Dewi, D. L., ... Ishii, H. (2015). Embryonic MicroRNA-369 controls metabolic splicing factors and urges cellular reprograming. PLoS One, 10(7), [e0132789]. https://doi.org/10.1371/journal.pone.0132789

Embryonic MicroRNA-369 controls metabolic splicing factors and urges cellular reprograming. / Konno, Masamitsu; Koseki, Jun; Kawamoto, Koichi; Nishida, Naohiro; Matsui, Hidetoshi; Dewi, Dyah Laksmi; Ozaki, Miyuki; Noguchi, Yuko; Mimori, Koshi; Gotoh, Noriko; Tanuma, Nobuhiro; Shima, Hiroshi; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi.

In: PLoS One, Vol. 10, No. 7, e0132789, 15.07.2015.

Research output: Contribution to journalArticle

Konno, M, Koseki, J, Kawamoto, K, Nishida, N, Matsui, H, Dewi, DL, Ozaki, M, Noguchi, Y, Mimori, K, Gotoh, N, Tanuma, N, Shima, H, Doki, Y, Mori, M & Ishii, H 2015, 'Embryonic MicroRNA-369 controls metabolic splicing factors and urges cellular reprograming', PLoS One, vol. 10, no. 7, e0132789. https://doi.org/10.1371/journal.pone.0132789
Konno M, Koseki J, Kawamoto K, Nishida N, Matsui H, Dewi DL et al. Embryonic MicroRNA-369 controls metabolic splicing factors and urges cellular reprograming. PLoS One. 2015 Jul 15;10(7). e0132789. https://doi.org/10.1371/journal.pone.0132789
Konno, Masamitsu ; Koseki, Jun ; Kawamoto, Koichi ; Nishida, Naohiro ; Matsui, Hidetoshi ; Dewi, Dyah Laksmi ; Ozaki, Miyuki ; Noguchi, Yuko ; Mimori, Koshi ; Gotoh, Noriko ; Tanuma, Nobuhiro ; Shima, Hiroshi ; Doki, Yuichiro ; Mori, Masaki ; Ishii, Hideshi. / Embryonic MicroRNA-369 controls metabolic splicing factors and urges cellular reprograming. In: PLoS One. 2015 ; Vol. 10, No. 7.
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