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

作者：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

来源：PLos One, 2015, 10(7): e0132789.

DOI：10.1371/journal.pone.0132789

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.

• 出版日期2015-7-15