Both circular RNAs (circRNAs) and cancer stem cells (CSCs) are separately known to be involved in cancer, but their interaction remains unclear. Here, the regulation of hepatocellular CSC self-renewal is discovered by a circRNA, circ-MALAT1, which is produced by back-splicing of a long noncoding RNA, MALAT1. Circ-MALAT1 is highly expressed in CSCs from clinical hepatocellular carcinoma samples under the mediation of an RNA-binding protein, AUF1. Surprisingly, circMALAT1 functions as a brake in ribosomes to retard PAX5 mRNA translation and promote CSCs' self-renewal by forming an unprecedented ternary complex with both ribosomes and mRNA. The discovered braking mechanism of a circRNA, termed mRNA braking, along with its more traditional role of miRNA sponging, uncovers a dual-faceted pattern of circRNA-mediated post-transcriptional regulation for maintaining a specific cell state.
Keywords: PAX5; circular RNA; hepatocellular cancer stem cells; miR‐6887‐3p; ribosomes; self‐renewal.
© 2019 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.