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

Qinyu Hao, Xinying Zong, Qinyu Sun, Yo Chuen Lin, You Jin Song, Seyedsasan Hashemikhabir, Rosaline Y.C. 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 M. Jenkins, Hans E. Johansson, Yuelin J. ZhuSven Diederichs, Anindya Bagchi, Tae Hoon Kim, Sarath C. Janga, Ashish Lal, Supriya G. Prasanth, Kannanganattu V. Prasanth

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere55102
Pages (from-to)1-33
Number of pages33
JournaleLife
Volume9
DOIs
StatePublished - Oct 2020

Bibliographical note

Funding Information:
We thank members of Prasanth’s laboratory for their valuable comments. We thank Drs. Sayee Anak (UIUC) (YAP antibody), Erik Bolton (UIUC) (Cyclin D1 antibody), Kun-Liang Guan (UCSD) (CTGF-promoter reporter constructs), Dr. Kenneth Irvine (Rutgers University (pTRIPZ-EGFP:WTIP)) for providing reagents, and Dr. Alvaro G Hernandez (UIUC Genomic facility) for RNA-sequencing. We also thank Dr. Jian Ma, Dr. Yang Zhang and Omid Gholamalamdari for technical discussion relating to bioinfor-matic analyses. We thank Jon Zetterval for his assistance on the Xenograft experiments. This work was supported by National Institute of Health [R01GM088252, R01GM132458 and R21AG065748 to KVP, GM125196 to SGP and GM123314 to SCJ], Cancer center at Illinois seed grant and Prairie Dragon Paddlers to KVP, National Science Foundation [EAGER grant to KVP {1723008} and career award {1243372} and 1818286 to SGP]. AL was supported by the Intramural Research Program of the National Cancer Institute (NCI), Center for Cancer Research (CCR). Research in the SD lab is supported by Deutsche Forschungsgemeinschaft (Di 1421/7–1) and Deutsche Krebshilfe.

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