LncRNA OIP5-AS1/cyrano suppresses GAK expression to control mitosis
Metrics: PDF 948 views | HTML 1577 views | ?
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
Jiyoung Kim, email: firstname.lastname@example.org
Myriam Gorospe, email: email@example.com
Keywords: lncRNA, proliferation, mitosis
Received: January 22, 2017 Accepted: March 22, 2017 Published: April 19, 2017
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.