4.7 Article

Long Noncoding RNA Lx8-SINE B2 Interacts with Eno1 to Regulate Self-Renewal and Metabolism of Embryonic Stem Cells

Journal

STEM CELLS
Volume 40, Issue 12, Pages 1094-1106

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/stmcls/sxac067

Keywords

embryonic stem cells (ESCs); self-renewal; cell cycle; pluripotency

Funding

  1. National Natural Science Foundation of China [31871488]
  2. National Key Research & Development Program of China [2018YFA0107000]
  3. China Postdoctoral Science Foundation [2021M701786]

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In this study, lncRNA Lx8-SINE B2 was identified as a novel regulator of ESC proliferation, cell cycle, and metabolism through working with Eno1.
Long noncoding RNAs (lncRNAs) emerge as important orchestrators of biological processes in embryonic stem cells (ESCs). LncRNA Lx8-SINE B2 was recently identified as an ESC-specific lncRNA that marks pluripotency. Here, we studied the function of lncRNA Lx8-SINE B2 in ESCs. Depletion of Lx8-SINE B2 disrupted ESC proliferation, repressed the expression of pluripotency genes, activated differentiation genes, and inhibited reprogramming to induced pluripotent stem cells. The reduction of the colony formation ability of ESCs upon Lx8-SINE B2 knockdown was accompanied by the elongation of the G1 phase and the shortening of the S phase. Transcriptome analysis revealed that Lx8-SINE B2 deficiency affected multiple metabolic pathways, particularly glycolysis. Mechanistically, Lx8-SINE B2 functions as a cytoplasmic lncRNA and interacts with the glycolytic enzyme Eno1 as shown by RNA pull-down and RNA localization analysis. Lx8-SINE B2 and Eno1 interact with and regulate each other's expression, hence promoting the expression of metabolic genes and influencing glycolysis. In conclusion, we have identified lncRNA Lx8-SINE B2 as a novel regulator of ESC proliferation, cell cycle, and metabolism through working with Eno1.

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