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

Jiyoung Kim1, Kotb Abdelmohsen1, Xiaoling Yang1

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

Nucleic Acids Research
|January 29, 2016
PubMed

Insights

Long noncoding RNA OIP5-AS1 acts as a competing endogenous RNA (ceRNA) by sponging the HuR protein. This interaction reduces cell proliferation by limiting HuR

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Biology

Background:

  • The functions of most mammalian long noncoding RNAs (lncRNAs) are not well understood.
  • lncRNAs play crucial roles in various biological processes, including cell proliferation.

Purpose of the Study:

  • To investigate the function of the abundant mammalian lncRNA OIP5-AS1.
  • To elucidate the regulatory mechanism of OIP5-AS1 in cell proliferation.

Main Methods:

  • Analysis of OIP5-AS1 expression and function in human cervical carcinoma HeLa cells.
  • RNA immunoprecipitation assays to identify interacting proteins and RNAs.
  • MS2 hairpin tagging to identify associated microRNAs.
  • Assessment of HuR-target mRNA interactions.

Main Results:

  • OIP5-AS1 was found to reduce cell proliferation.
  • The RNA-binding protein HuR, a promoter of cell proliferation, binds and stabilizes OIP5-AS1.
  • MicroRNA miR-424 interacts with OIP5-AS1, competing with HuR for binding.
  • OIP5-AS1 acts as a competing endogenous RNA (ceRNA) or 'sponge' for HuR, sequestering it from its target mRNAs involved in proliferation.

Conclusions:

  • OIP5-AS1 functions as a ceRNA for HuR, inhibiting its availability to target mRNAs.
  • This mechanism represses HuR-mediated cell proliferation.
  • OIP5-AS1 represents a novel regulatory factor in controlling cell proliferation through lncRNA-protein-mRNA interactions.

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