<i>LAST</i>, a c-Myc-inducible long noncoding RNA, cooperates with CNBP to promote <i>CCND1</i> mRNA stability in human cells.

Abstract

Cyclin D1 is a critical regulator of cell cycle progression and works at the G1 to S-phase transition. Here, we report the isolation and characterization of the novel c-Myc-regulated lncRNA <i>LAST</i> (<u>L</u>ncRNA-<u>A</u>ssisted <u>S</u>tabilization of <u>T</u>ranscripts), which acts as a <i>CCND1</i> mRNA stabilizer. Mechanistically, <i>LAST</i> was shown to cooperate with CNBP to bind to the 5'UTR of <i>CCND1</i> mRNA to protect against possible nuclease targeting. In addition, data from CNBP RIP-seq and <i>LAST</i> RNA-seq showed that <i>CCND1</i> mRNA might not be the only target of <i>LAST</i> and CNBP; three additional mRNAs were shown to be post-transcriptional targets of <i>LAST</i> and CNBP. In a xenograft model, depletion of <i>LAST</i> diminished and ectopic expression of <i>LAST</i> induced tumor formation, which are suggestive of its oncogenic function. We thus report a previously unknown lncRNA involved in the fine-tuned regulation of <i>CCND1</i> mRNA stability, without which <i>CCND1</i> exhibits, at most, partial expression.