The S-phase-induced lncRNA SUNO1 promotes cell proliferation by controlling YAP1/Hippo signaling pathway

Elife. 2020 Oct 27:9:e55102. doi: 10.7554/eLife.55102.

Abstract

Cell cycle is a cellular process that is subject to stringent control. In contrast to the wealth of knowledge of proteins controlling the cell cycle, very little is known about the molecular role of lncRNAs (long noncoding RNAs) in cell-cycle progression. By performing genome-wide transcriptome analyses in cell-cycle-synchronized cells, we observed cell-cycle phase-specific induction of >2000 lncRNAs. Further, we demonstrate that an S-phase-upregulated lncRNA, SUNO1, facilitates cell-cycle progression by promoting YAP1-mediated gene expression. SUNO1 facilitates the cell-cycle-specific transcription of WTIP, a positive regulator of YAP1, by promoting the co-activator, DDX5-mediated stabilization of RNA polymerase II on chromatin. Finally, elevated SUNO1 levels are associated with poor cancer prognosis and tumorigenicity, implying its pro-survival role. Thus, we demonstrate the role of a S-phase up-regulated lncRNA in cell-cycle progression via modulating the expression of genes controlling cell proliferation.

Keywords: HCT116; U2OS; WTIP; cell cycle; chromosomes; gene expression; human cancer cell lines; lncRNA; none.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Proliferation / genetics*
  • Co-Repressor Proteins / genetics*
  • Co-Repressor Proteins / metabolism
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • DEAD-box RNA Helicases / genetics*
  • DEAD-box RNA Helicases / metabolism
  • Gene Expression Regulation*
  • HCT116 Cells
  • HeLa Cells
  • Humans
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • S Phase
  • Signal Transduction / physiology*
  • Up-Regulation

Substances

  • Co-Repressor Proteins
  • Cytoskeletal Proteins
  • RNA, Long Noncoding
  • WTIP protein, human
  • Ddx5 protein, human
  • DEAD-box RNA Helicases

Associated data

  • GEO/GSE143275
  • GEO/GSE157393