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2016 ; 44
(5
): 2378-92
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LncRNA OIP5-AS1/cyrano sponges RNA-binding protein HuR
#MMPMID26819413
Kim J
; Abdelmohsen K
; Yang X
; De S
; Grammatikakis I
; Noh JH
; Gorospe M
Nucleic Acids Res
2016[Mar]; 44
(5
): 2378-92
PMID26819413
show ga
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.
|*Gene Expression Regulation
[MESH]
|ADAM Proteins/genetics/metabolism
[MESH]
|Base Sequence
[MESH]
|Binding Sites
[MESH]
|Binding, Competitive
[MESH]
|Cell Proliferation/genetics
[MESH]
|ELAV-Like Protein 1/antagonists & inhibitors/*genetics/metabolism
[MESH]
|HeLa Cells
[MESH]
|Humans
[MESH]
|Membrane Proteins/genetics/metabolism
[MESH]
|MicroRNAs/*genetics/metabolism
[MESH]
|Molecular Sequence Data
[MESH]
|Protein Binding
[MESH]
|RNA, Long Noncoding/*genetics/metabolism
[MESH]
|RNA, Messenger/*genetics/metabolism
[MESH]
|RNA, Small Interfering/genetics/metabolism
[MESH]