Oncotarget

Research Papers:

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

Jiyoung Kim _, Ji Heon Noh, Seung-Kyu Lee, Rachel Munk, Alexei Sharov, Elin Lehrmann, Yongqing Zhang, Weidong Wang, Kotb Abdelmohsen and Myriam Gorospe

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Oncotarget. 2017; 8:49409-49420. https://doi.org/10.18632/oncotarget.17219

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Abstract

Jiyoung Kim1, Ji Heon Noh1, Seung-Kyu Lee1, Rachel Munk1, Alexei Sharov1, Elin Lehrmann1, Yongqing Zhang1, Weidong Wang1, Kotb Abdelmohsen1 and Myriam Gorospe1

1Laboratory of Genetics and Genomics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, MD 21224, USA

Correspondence to:

Jiyoung Kim, email: kim.jiyoung@elixirgen.com

Myriam Gorospe, email: myriam-gorospe@nih.gov

Keywords: lncRNA, proliferation, mitosis

Received: January 22, 2017     Accepted: March 22, 2017     Published: April 19, 2017

ABSTRACT

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.


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