The cancer transcriptome is remarkably complex, including low-abundance transcripts, many not polyadenylated. To fully characterize the transcriptome of localized prostate cancer, we performed ultradeep total RNA-seq on 144 tumors with rich clinical annotation. This revealed a linear transcriptomic subtype associated with the aggressive intraductal carcinoma sub-histology and a fusion profile that differentiates localized from metastatic disease. Analysis of back-splicing events showed widespread RNA circularization, with the average tumor expressing 7,232 circular RNAs (circRNAs). The degree of circRNA production was correlated to disease progression in multiple patient cohorts. Loss-offunction screening identified 11.3% of highly abundant circRNAs as essential for cell proliferation; for 90% of these, their parental linear transcripts were not essential. Individual circRNAs can have distinct functions, with circCSNK1G3 promoting cell growth by interacting with miR-181. These data advocate for adoption of ultra-deep RNA-seq without poly-A selection to interrogate both linear and circular transcriptomes.

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Journal Cell
Chen, S.-J, Huang, V, Xu, X., Livingstone, J., Soares, F., Jeon, J, … Hansen He, H. (2019). Widespread and Functional RNA Circularization in Localized Prostate Cancer. Cell, 176(4), 831–83+. doi:10.1016/j.cell.2019.01.025