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Distinct Processing of lncRNAs Contributes to Non-conserved Functions in Stem Cells
Chun-Jie Guo1, Xu-Kai Ma2, Yu-Hang Xing1
1State 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.
Cell
|April 8, 2020
Summary
Long noncoding RNAs (lncRNAs) rapidly evolve. This study reveals that human and mouse embryonic stem cells (ESCs) process and localize lncRNAs differently, impacting pluripotency and WNT signaling.
Area of Science:
- Molecular Biology
- Genetics
- Developmental Biology
Background:
- Long noncoding RNAs (lncRNAs) exhibit rapid evolution compared to messenger RNAs (mRNAs).
- The conservation of lncRNA processing, subcellular localization, and function across species remains largely uninvestigated.
- Embryonic stem cell (ESC) pluripotency is a critical area of developmental biology research.
Purpose of the Study:
- To investigate whether conserved lncRNAs undergo conserved processing, localization, and function.
- To compare the subcellular localization of lncRNAs in human ESCs (hESCs) and mouse ESCs (mESCs).
- To elucidate the functional significance of differential lncRNA localization in hESC pluripotency.
Main Methods:
- Comparative analysis of lncRNA subcellular localization in hESCs and mESCs.
- Investigating the role of the lncRNA FAST (specifically hFAST and mFast) in ESCs.
- Identifying protein-protein interactions involving hFAST and its impact on WNT signaling pathways.
- Examining the regulation of mFast processing by splicing factors like PPIE.
Main Results:
- A significantly higher proportion of lncRNAs are found in the cytoplasm of hESCs compared to mESCs.
- The positionally conserved lncRNA FAST shows divergent processing and localization between hESCs and mESCs.
- Cytoplasmic hFAST interacts with β-TrCP, inhibiting β-catenin degradation and activating WNT signaling essential for hESC pluripotency.
- Nuclear-retained mFast processing is suppressed by the splicing factor PPIE, which is highly expressed in mESCs.
Conclusions:
- lncRNA processing and subcellular localization are crucial, yet under-appreciated, factors in the rapid functional evolution of lncRNAs.
- Differential lncRNA localization plays a significant role in maintaining ESC pluripotency.
- Species-specific regulation of lncRNA function contributes to evolutionary divergence.
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