Frontiers in Cell and Developmental Biology (Jun 2020)

LncPrep + 96kb 2.2 kb Inhibits Estradiol Secretion From Granulosa Cells by Inducing EDF1 Translocation

  • Fen Feng,
  • Jing Wang,
  • Riqiang Bao,
  • Long Li,
  • Xiating Tong,
  • Suo Han,
  • Hongdan Zhang,
  • Weihui Wen,
  • Li Xiao,
  • Chunping Zhang

DOI
https://doi.org/10.3389/fcell.2020.00481
Journal volume & issue
Vol. 8

Abstract

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LncPrep + 96kb is a novel long non-coding RNA expressed in murine granulosa cells with two transcripts that are 2.2 and 2.8 kb in length. However, the potential roles of lncPrep + 96kb in granulosa cells remain poorly understood. In this study, we investigated the effect of the lncPrep + 96kb 2.2 kb transcript on granulosa cells through the overexpression and knockdown of lncPrep + 96kb 2.2 kb. We found that lncPrep + 96kb 2.2 kb inhibited aromatase expression and estradiol production. Endothelial differentiation-related factor 1 (EDF1) is an evolutionarily conserved transcriptional coactivator. We found that EDF1 knockdown inhibited aromatase expression and estradiol production. The RNA immunoprecipitation results also showed that lncPrep + 96kb 2.2 kb can bind to EDF1 and that overexpression of lncPrep + 96kb 2.2 kb induced the translocation of EDF1 from the nucleus to the cytoplasm. The CatRAPID signature revealed that the 1,979–2,077 and 603–690 nucleotide positions in lncPrep + 96kb 2.2 kb were potential binding sites for EDF1. We found that mutating the 1,979–2,077 site rescued the effects of lncPrep + 96kb 2.2 kb on aromatase expression and estradiol production. In conclusion, we are the first to report that specific expression of lncPrep + 96kb 2.2 kb in granulosa cells inhibits the production of estradiol by influencing the localization of EDF1 in granulosa cells. The 1,979–2,077 site of lncPrep + 96kb 2.2 kb contributes to the ability to bind to EDF1.

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