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

ABSTRACT: Long noncoding RNAs (lncRNAs) have been found to regulate the expression of mRNAs with which they share partial complementarity. 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 cells revealed the appearance of many aberrant (monopolar, multipolar, misaligned) mitotic spindles. By biotin-oligomer affinity pulldown, proteomic, and bioinformatic analyses, we identified a subset of human cell cycle regulatory proteins encoded by mRNAs that were capable of interacting with OIP5-AS1. Further investigation revealed that GAK mRNA, which encodes a cyclin G-associated kinase important for mitotic progression, was a prominent target of 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 was caused by an untimely rise in GAK levels and suggest that OIP5-AS1 suppresses cell proliferation at least in part by reducing GAK levels

ORGANISM(S): Homo sapiens

PROVIDER: GSE93551 | GEO | 2017/09/25

SECONDARY ACCESSION(S): PRJNA361083

REPOSITORIES: GEO

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