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

期诱导的 lncRNA SUNO1 通过控制 YAP1/Hippo 信号通路促进细胞增殖

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作者:Qinyu Hao #, Xinying Zong #, Qinyu Sun, Yo-Chuen Lin, You Jin Song, Seyedsasan Hashemikhabir, Rosaline Yc Hsu, Mohammad Kamran, Ritu Chaudhary, Vidisha Tripathi, Deepak Kumar Singh, Arindam Chakraborty, Xiao Ling Li, Yoon Jung Kim, Arturo V Orjalo, Maria Polycarpou-Schwarz, Branden S Moriarity, Lisa

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.

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