One of the most unexpected discoveries in the genomics era of biology is the extensive transcription of RNA from non-protein-coding regions of the genome ( Tens of thousands of long noncoding RNAs (lncRNAs), defined as transcripts larger than 200 nt with no or low protein-coding potential, have been identified in mammalian cells. Thus, characterization of the genome-wide changes in the transcriptional program during the cell cycle is a critical step toward a deeper mechanistic understanding of the cell proliferation process and its role in cancer. Understanding the mode of cell cycle-regulated gene expression is also central to the study of many diseases, most prominently cancer. Extensive studies on the identification of protein-coding genes exhibiting periodic expression patterns during cell cycle have led to improved understanding of the basic cell-cycle process and its regulatory mechanism, exemplified by studies on cyclins ( Pines and Hunter, 1989). For example, studies have established the role of transcription factors (TFs) such as the E2F and TEAD family of proteins in regulating the transcription of genes controlling cell cycle and cell proliferation ( Frolov and Dyson, 2004 Chen et al., 2009 Harbour and Dean, 2000 Meng et al., 2016). Such dynamic changes in gene expression during cell cycle are essential for efficient cell-cycle progression ( Robertson et al., 1990 Cho et al., 2001 Dyson, 1998 Frolov and Dyson, 2004 Sánchez and Dynlacht, 1996). The activity of genes that control cell proliferation is strictly regulated through the cell-cycle-dependent oscillation of their expression ( Robertson et al., 1990 Cho et al., 2001 Dyson, 1998 Frolov and Dyson, 2004 Sánchez and Dynlacht, 1996). The eukaryotic cell cycle is controlled by a regulatory network, which proceeds through tightly regulated transitions to make sure that specific events occur in an orderly fashion. IntroductionĬell-cycle progression is a vital cellular process, subject to stringent control, as aberrant cell-cycle progression usually results in genome instability, contributing to cancer progression ( Robertson et al., 1990 Cho et al., 2001 Dyson, 1998 Frolov and Dyson, 2004 Sánchez and Dynlacht, 1996).
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. Finally, elevated SUNO1 levels are associated with poor cancer prognosis and tumorigenicity, implying its pro-survival role. 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. Further, we demonstrate that an S-phase-upregulated lncRNA, SUNO1, facilitates cell-cycle progression by promoting YAP1-mediated gene expression. By performing genome-wide transcriptome analyses in cell-cycle-synchronized cells, we observed cell-cycle phase-specific induction of >2000 lncRNAs. 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.