Embryonic MicroRNA-369 Controls Metabolic Splicing Factors and Urges Cellular Reprograming
Author(s) -
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
Publication year - 2015
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0132789
Subject(s) - biology , reprogramming , microbiology and biotechnology , embryonic stem cell , gene knockdown , induced pluripotent stem cell , chromatin , cellular differentiation , microrna , chromatin immunoprecipitation , gene silencing , genetics , gene expression , cell , cell culture , gene , promoter
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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