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Some long noncoding RNAs (lncRNAs) can regulate gene expression programs, in turn affecting specific cellular processes. We sought to identify the mechanism through which the lncRNA OIP5-AS1, which is abundant in the cytoplasm, suppressed cell proliferation. Silencing of OIP5-AS1 in human cervical carcinoma HeLa cells triggered the appearance of many aberrant (monopolar, multipolar, misaligned) mitotic spindles. Through a combination of approaches to pull down mRNAs bound to OIP5-AS1 and identify proteins differentially expressed when OIP5-AS1 was silenced, we identified a subset of human cell cycle regulatory proteins encoded by mRNAs that interacted with OIP5-AS1 in HeLa cells. Further analysis revealed that GAK mRNA, which encodes a cyclin G-associated kinase important for mitotic progression, associated prominently with OIP5-AS1. The interaction between these two transcripts led to a reduction in GAK mRNA stability and GAK protein abundance, as determined in cells in which OIP5-AS1 levels were increased or decreased. Importantly, the aberrant mitotic cell division seen after silencing OIP5-AS1 was partly rescued if GAK was simultaneously silenced. These findings indicate that the abnormal mitoses seen after silencing OIP5-AS1 were caused by an untimely rise in GAK levels and suggest that OIP5-AS1 suppresses cell proliferation at least in part by reducing GAK levels.

LncRNA OIP5-AS1/cyrano suppresses GAK expression to control mitosis