LncRNA OIP5-AS1/cyrano sponges RNA-binding protein HuR.
LncRNA OIP5-AS1/cyrano sponges RNA-binding protein HuR.
复制标题
lncRNA OIP5-AS1/Cyrano海绵RNA结合蛋白HUR。
DOI：
10.1093/nar/gkw017
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发表时间：
2016-03-18
影响因子：
14.9
通讯作者：
Gorospe M
中科院分区：
文献类型：
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作者：
Kim J;Abdelmohsen K;Yang X;De S;Grammatikakis I;Noh JH;Gorospe M
绝大多数哺乳动物长链非编码RNA（lnc）的功能仍然未知。在这里，对一种高度丰富的哺乳动物lncRNA OIP 5-AS 1（在斑马鱼中被称为cyrano）的分析表明，OIP 5-AS 1可以减少细胞增殖。在人宫颈癌HeLa细胞中，促进细胞增殖的RNA结合蛋白HuR与OIP 5-AS 1结合并稳定OIP 5-AS 1。用MS 2发夹标记OIP 5-AS 1以鉴定相关microRNA，表明miR-424与OIP 5-AS 1相互作用并与HuR竞争结合OIP 5-AS 1。我们进一步鉴定了OIP 5-AS 1的“海绵”功能，因为高水平的OIP 5-AS 1增加了HuR-OIP 5-AS 1复合物并阻止了HuR与靶mRNA的相互作用，包括编码增殖蛋白的那些，而相反，降低OIP 5-AS 1增加了HuR与靶mRNA复合物的丰度。我们提出OIP 5-AS 1作为海绵或竞争性内源性（ce）RNA的HuR，限制其可用性HuR靶mRNA，从而抑制HuR引起的增殖表型。
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.