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...
Main Authors: | , , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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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. |
first_indexed | 2024-04-12T03:33:11Z |
format | Article |
id | doaj.art-620a9c84b7214c579c6ea5dee3bd99d3 |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-04-12T03:33:11Z |
publishDate | 2015-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
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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