論文

査読有り 国際誌
2018年

The DEAD-box RNA-binding protein DDX6 regulates parental RNA decay for cellular reprogramming to pluripotency.

PloS one
  • Daisuke Kami
  • ,
  • Tomoya Kitani
  • ,
  • Akihiro Nakamura
  • ,
  • Naoki Wakui
  • ,
  • Rena Mizutani
  • ,
  • Masahito Ohue
  • ,
  • Fuyuki Kametani
  • ,
  • Nobuyoshi Akimitsu
  • ,
  • Satoshi Gojo

13
10
開始ページ
e0203708
終了ページ
記述言語
英語
掲載種別
DOI
10.1371/journal.pone.0203708

Cellular transitions and differentiation processes require mRNAs supporting the new phenotype but also the clearance of existing mRNAs for the parental phenotype. Cellular reprogramming from fibroblasts to induced pluripotent stem cells (iPSCs) occurs at the early stage of mesenchymal epithelial transition (MET) and involves drastic morphological changes. We examined the molecular mechanism for MET, focusing on RNA metabolism. DDX6, an RNA helicase, was indispensable for iPSC formation, in addition to RO60 and RNY1, a non-coding RNA, which form complexes involved in intracellular nucleotide sensing. RO60/RNY1/DDX6 complexes formed prior to processing body formation, which is central to RNA metabolism. The abrogation of DDX6 expression inhibited iPSC generation, which was mediated by RNA decay targeting parental mRNAs supporting mesenchymal phenotypes, along with microRNAs, such as miR-302b-3p. These results show that parental mRNA clearance is a prerequisite for cellular reprogramming and that DDX6 plays a central role in this process.

リンク情報
DOI
https://doi.org/10.1371/journal.pone.0203708
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30273347
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166933

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