Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1

By K. Abdelmohsen, Amaresh Chandra Panda, R. Munk, Ioannis Grammatikakis, D. Dudekula, Supriyo De, Jiyoung Kim, J. Noh, Kyoung Mi Kim, J. Martindale and 1 more. RNA Biology, 2017

745 citations recorded by the source corpus.

ABSTRACT 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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/8a598579be42f246a66577ddbb2c006b7c089262

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. B. Han
2. J. Chao
3. Honghong Yao

Citations in the corpus

• Circular RNA and its mechanisms in disease: From the bench to the clinic. (2018, background): “circPABPN1 and PABPN1 mRNA competitively bind to HuR, and the combination of circPABPN1 and HuR subsequently suppresses PABPN1 translation (Abdelmohsen et al., 2017).”
• Circular RNAs: Promising Biomarkers for Human Diseases (2018, background): “CircPABPN1 suppresses PABPN1 translation by competitively binding toHuR preventing interaction between HuR with PABPN1 miRNA [23].”
• Circular RNA-protein interactions: functions, mechanisms, and identification (2020, background): “first reported competition between circPABPN1 and its cognate mRNA for the RPB, Hu-antigen R (HuR) [53].”
• Circular RNA: metabolism, functions and interactions with proteins (2020, background): “In addition to disrupting the splicing factor network, circPABPN1 sequesters HuR that stabilizes polyadenosine binding protein nuclear 1 (PABPN1) mRNA, consequently lowering PABPN1 levels and inhibiting HeLa cell proliferation [109].”