Function of promoter-associated non-coding RNA for the epigenome formation in the early mouse embryo

2014 Fiscal Year Final Research Report

• Project/Area Number: 25660250
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Integrative animal science
• Research Institution: Kyushu University
• Principal Investigator: IMAMURA TAKUYA 九州大学, 医学(系)研究科(研究院), 助教 (90390682)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: ノンコーディングRNA / DNAメチル化 / DNA脱メチル化 / 遺伝子活性化 / 人為操作胚 / 雌性発生胚

Outline of Final Research Achievements

In mice, zygotic activation occurs for a wide variety of genes, mainly at the 2-cell stage. In this study, directional RNA-seq of MII oocytes and 2-cell embryos identified more than 1000 divergently transcribed long noncoding RNA (lncRNA)/mRNA gene pairs. Expression of these bidirectional promoter-associated noncoding RNAs (pancRNAs) was strongly associated with the upregulation of their cognate genes. Conversely, knockdown of three abundant pancRNAs led to reduced mRNA expression, accompanied by sustained DNA methylation even in the presence of enzymes responsible for DNA demethylation. In particular, microinjection of siRNA against the abundant pancRNA partner of interleukin 17d (Il17d) mRNA at the 1-cell stage caused embryonic lethality, which was rescued by supplying IL17D protein in vitro at the 4-cell stage. Thus, this novel class of lncRNAs can modulate the epigenetic machinery in cis to activate zygotic genes and is essential for preimplantation development.

Free Research Field

分子遺伝学