LncRNA OIP5-AS1/cyrano sponges RNA-binding protein HuR

J Kim, K Abdelmohsen, X Yang, S De… - Nucleic acids …, 2016 - academic.oup.com
J Kim, K Abdelmohsen, X Yang, S De, I Grammatikakis, JH Noh, M Gorospe
Nucleic acids research, 2016academic.oup.com
The function of the vast majority of mammalian long noncoding (lnc) RNAs remains
unknown. Here, analysis of a highly abundant mammalian lncRNA, OIP5-AS1, known as
cyrano in zebrafish, revealed that OIP5-AS1 reduces cell proliferation. In human cervical
carcinoma HeLa cells, the RNA-binding protein HuR, which enhances cell proliferation,
associated with OIP5-AS1 and stabilized it. Tagging OIP5-AS1 with MS2 hairpins to identify
associated microRNAs revealed that miR-424 interacted with OIP5-AS1 and competed with …
Abstract
The function of the vast majority of mammalian long noncoding (lnc) RNAs remains unknown. Here, analysis of a highly abundant mammalian lncRNA, OIP5-AS1, known as cyrano in zebrafish, revealed that OIP5-AS1 reduces cell proliferation. In human cervical carcinoma HeLa cells, the RNA-binding protein HuR, which enhances cell proliferation, associated with OIP5-AS1 and stabilized it. Tagging OIP5-AS1 with MS2 hairpins to identify associated microRNAs revealed that miR-424 interacted with OIP5-AS1 and competed with HuR for binding to OIP5-AS1. We further identified a ‘sponge’ function for OIP5-AS1, as high levels of OIP5-AS1 increased HuR-OIP5-AS1 complexes and prevented HuR interaction with target mRNAs, including those that encoded proliferative proteins, while conversely, lowering OIP5-AS1 increased the abundance of HuR complexes with target mRNAs. We propose that OIP5-AS1 serves as a sponge or a competing endogenous (ce)RNA for HuR, restricting its availability to HuR target mRNAs and thereby repressing HuR-elicited proliferative phenotypes.
Oxford University Press
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