Effect of extracellular spliceosomal snRNAs on the transcriptome of ovarian cancer cells

Exogenous signals from drug-stressed cancer cells accelerate the proliferation of neighboring tumor cells and promote to acquire a more aggressive phenotype. We have recently found an exciting phenomenon: drug-stressed cancer cells secrete various components of the spliceosome: proteins and a number of snRNAs. We have observed this phenomenon both in vitro (culture media from cancer cell lines [Pavluykov M. et al., 2018]) and in vivo (ovarian cancer ascites after chemotherapy [Shender V. et al., 2014]). The aim of this study was to elucidate the role of secreted spliceosomal snRNAs in intercellular communication. We constructed synthetic U12 and U6atac snRNAs close to the natural structure, including some non-canonical nucleotides imitating post-transcriptional RNA modifications. RNAseq analysis of SKOV3 cells transfected with U6atac or U12 snRNA analogs has shown that both exogenous snRNAs lead to an increase of abundance of proteins related to cell cycle regulation and M phase. It has been recently shown that a number of spliceosomal proteins affect regulation of the cell cycle, in particular the M phase [Maslon et al., 2014]. Here we demonstrated that not only spliceosomal proteins but also spliceosomal snRNAs (U12 and U6atac) affect cell cycle gene expression. This study revealed previously unknown signaling molecules in the microenvironment of ovarian cancer that have potential clinical significance. Overall design: SKOV3 cells were transfected with in vitro synthesized snRNAs: U12, U6atac snRNAs, or a control GFP mRNA fragment (89 nucleotides). SKOV3 cells treated with empty transfectant were taken as a contol. Transcriptomic profiling was performed 48 h after transfection.