Recurrent Chimeric RNA, CTNNBIP1-CLSTN1 Regulates Cell Proliferation through SERPINE2 in Non-neoplastic Human Cells

Conventional wisdom that chimeric RNAs and proteins being peculiarity of carcinoma is being challenged, as more evidence are accumulated supporting that chimeric RNAs are widely spread in noncancerous tissues and cells. One particular chimeric RNA, CTNNBIP1-CLSTN1 produced by cis-splicing between two neighboring genes, has been detected in a variety of normal tissues. However, the details of its functionality are not clear. Here, we report that this fusion transcript is expressed in almost all tissues, and a wide range of cell types including fibroblasts, epithelial, stem, vascular endothelial cells, and hepatocytes. The expression level in non-cancerous cell lines is also not evidently different from that in the cancer cell lines. Furthermore, silencing CTNNBIP1-CLSTN1 significantly reduces cell proliferation rate, by inducing G2/M arrest in cell cycle progress and apoptosis in at least three cell types. Importantly, rescue experiments confirmed that the cell cycle arrest can be regained by exogenous expression of the chimera, but not the wild type parental gene. Further evidence is provided that CTNNBIP1-CLSTN1 regulates cell proliferation through SERPINE2. In conclusion, CTNNBIP1-CLSTN1 chimeric transcript widely exists in normal physiology, and undertakes essential cellular maintenance roles. It represents an example of a new class of fusion RNA, dubbed “housekeeping chimeric RNAs”. analyzing differential gene expression in control and CTNNBIP1-CLSTN1 knocking down cells