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In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
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Gene activation-associated long noncoding RNAs function in mouse preimplantation development.

Nobuhiko Hamazaki1, Masahiro Uesaka1, Kinichi Nakashima2

  • 1Department of Biophysics and Global COE Program, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwake, Sakyo-ku, Kyoto 606-8502, Japan Division of Basic Stem Cell Biology, Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

Development (Cambridge, England)
|January 31, 2015
PubMed
Summary
This summary is machine-generated.

Newly discovered bidirectional promoter-associated noncoding RNAs (pancRNAs) activate key zygotic genes during early mouse development. Their absence causes embryonic lethality, highlighting their crucial role in preimplantation development.

Keywords:
DNA demethylationEarly mouse preimplantation developmentEpigenetic regulationLong noncoding RNAPluripotencyZygotic gene activation

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Area of Science:

  • Developmental Biology
  • Epigenetics
  • Genomics

Background:

  • Zygotic gene activation (ZGA) initiates embryonic development, primarily at the 2-cell stage in mice.
  • Long noncoding RNAs (lncRNAs) are emerging as critical regulators of gene expression.
  • Understanding lncRNA roles in early development is essential for reproductive biology.

Purpose of the Study:

  • To identify and characterize novel lncRNAs involved in mouse zygotic gene activation.
  • To investigate the functional role of these lncRNAs in regulating gene expression and embryonic development.
  • To explore the epigenetic mechanisms underlying pancRNA-mediated gene regulation.

Main Methods:

  • Directional RNA sequencing (RNA-seq) of mouse MII oocytes and 2-cell embryos.
  • Identification and analysis of divergently transcribed lncRNA/mRNA gene pairs.
  • siRNA-mediated knockdown of specific pancRNAs and assessment of gene expression and DNA methylation.
  • In vitro rescue experiments using IL17D protein.

Main Results:

  • Over 1000 divergently transcribed lncRNA/mRNA pairs, termed pancRNAs, were identified.
  • pancRNA expression strongly correlated with the upregulation of their cognate genes.
  • Knockdown of pancRNAs resulted in decreased mRNA expression and sustained DNA methylation.
  • siRNA targeting of an Il17d-associated pancRNA caused embryonic lethality, rescued by IL17D protein.

Conclusions:

  • Bidirectional promoter-associated noncoding RNAs (pancRNAs) represent a novel class of lncRNAs.
  • pancRNAs modulate the transcription machinery in cis to activate zygotic genes.
  • These pancRNAs are essential for successful preimplantation development in mice.