Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1
Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1
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DOI：
10.1080/15476286.2017.1279788
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发表时间：
2017-01-01
期刊：
影响因子：
4.1
通讯作者：
Gorospe, Myriam
中科院分区：
文献类型：
--
作者：
Abdelmohsen, Kotb;Panda, Amaresh C.;Gorospe, Myriam
HUR通过与数百个编码和非编码的线性RNA结合来影响基因表达程序，从而影响细胞表型。然而，HUR是否与环状RNA结合并对其功能产生影响尚不清楚。在这里，我们已经在人宫颈癌HeLa细胞中发现了大量与Hur结合的CircRNAs。其中最突出的HUR靶标CircRNA之一是HSA_CIRC_0031288，因其起源于PABPN1前基因而被重新命名为CircPABPN1。进一步的分析表明，Hur不影响CircPABPN1的丰度；然而，有趣的是，高水平的CircPABPN1抑制了Hur与PABPN1 mRNA的结合。对PABPN1基因多聚体的分析表明，PABPN1的翻译受Hur正向调控，而受CircPABPN1负向调控。我们认为，CircPABPN1与Hur的广泛结合阻止了Hur与PABPN1 mRNA的结合，并降低了PABPN1的翻译水平，这为CircRNA及其同源mRNA之间竞争影响翻译的RBP提供了第一个例子。
HuR influences gene expression programs and hence cellular phenotypes by binding to hundreds of coding and noncoding linear RNAs. However, whether HuR binds to circular RNAs (circRNAs) and impacts on their function is unknown. Here, we have identified en masse circRNAs binding HuR in human cervical carcinoma HeLa cells. One of the most prominent HuR target circRNAs was hsa_circ_0031288, renamed CircPABPN1 as it arises from the PABPN1 pre-mRNA. Further analysis revealed that HuR did not influence CircPABPN1 abundance; interestingly, however, high levels of CircPABPN1 suppressed HuR binding to PABPN1 mRNA. Evaluation of PABPN1 mRNA polysomes indicated that PABPN1 translation was modulated positively by HuR and hence negatively by CircPABPN1. We propose that the extensive binding of CircPABPN1 to HuR prevents HuR binding to PABPN1 mRNA and lowers PABPN1 translation, providing the first example of competition between a circRNA and its cognate mRNA for an RBP that affects translation.