1. Academic Validation
  2. Distinct Processing of lncRNAs Contributes to Non-conserved Functions in Stem Cells

Distinct Processing of lncRNAs Contributes to Non-conserved Functions in Stem Cells

  • Cell. 2020 Apr 30;181(3):621-636.e22. doi: 10.1016/j.cell.2020.03.006.
Chun-Jie Guo 1 Xu-Kai Ma 2 Yu-Hang Xing 1 Chuan-Chuan Zheng 1 Yi-Feng Xu 1 Lin Shan 1 Jun Zhang 1 Shaohua Wang 3 Yangming Wang 3 Gordon G Carmichael 4 Li Yang 5 Ling-Ling Chen 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
  • 2 CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
  • 3 Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, 100871 Beijing, China.
  • 4 Department of Genetics and Genome Sciences, UCONN Health, Farmington, CT 06030, USA.
  • 5 CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai 201210, China.
  • 6 State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai 201210, China. Electronic address: [email protected].
Abstract

Long noncoding RNAs (lncRNAs) evolve more rapidly than mRNAs. Whether conserved lncRNAs undergo conserved processing, localization, and function remains unexplored. We report differing subcellular localization of lncRNAs in human and mouse embryonic stem cells (ESCs). A significantly higher fraction of lncRNAs is localized in the cytoplasm of hESCs than in mESCs. This turns out to be important for hESC pluripotency. FAST is a positionally conserved lncRNA but is not conserved in its processing and localization. In hESCs, cytoplasm-localized hFAST binds to the WD40 domain of the E3 ubiquitin ligase β-TrCP and blocks its interaction with phosphorylated β-catenin to prevent degradation, leading to activated Wnt signaling, required for pluripotency. In contrast, mFast is nuclear retained in mESCs, and its processing is suppressed by the splicing factor PPIE, which is highly expressed in mESCs but not hESCs. These findings reveal that lncRNA processing and localization are previously under-appreciated contributors to the rapid evolution of function.

Keywords

ESC; FAST; PPIE; RNA processing; WNT; conservation; embryonic stem cell; evolution; lncRNA; long noncoding RNA; splicing; subcellular localization.

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