Embryonic MicroRNA-369 Controls Metabolic Splicing Factors and Urges Cellular Reprograming.

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 histon...

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Main Authors: 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
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4503752?pdf=render
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author 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
author_facet 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
author_sort Masamitsu Konno
collection DOAJ
description 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.
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spelling doaj.art-620a9c84b7214c579c6ea5dee3bd99d32022-12-22T03:49:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01107e013278910.1371/journal.pone.0132789Embryonic MicroRNA-369 Controls Metabolic Splicing Factors and Urges Cellular Reprograming.Masamitsu KonnoJun KosekiKoichi KawamotoNaohiro NishidaHidetoshi MatsuiDyah Laksmi DewiMiyuki OzakiYuko NoguchiKoshi MimoriNoriko GotohNobuhiro TanumaHiroshi ShimaYuichiro DokiMasaki MoriHideshi IshiiNoncoding 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.http://europepmc.org/articles/PMC4503752?pdf=render
spellingShingle 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
Embryonic MicroRNA-369 Controls Metabolic Splicing Factors and Urges Cellular Reprograming.
PLoS ONE
title Embryonic MicroRNA-369 Controls Metabolic Splicing Factors and Urges Cellular Reprograming.
title_full Embryonic MicroRNA-369 Controls Metabolic Splicing Factors and Urges Cellular Reprograming.
title_fullStr Embryonic MicroRNA-369 Controls Metabolic Splicing Factors and Urges Cellular Reprograming.
title_full_unstemmed Embryonic MicroRNA-369 Controls Metabolic Splicing Factors and Urges Cellular Reprograming.
title_short Embryonic MicroRNA-369 Controls Metabolic Splicing Factors and Urges Cellular Reprograming.
title_sort embryonic microrna 369 controls metabolic splicing factors and urges cellular reprograming
url http://europepmc.org/articles/PMC4503752?pdf=render
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