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

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...

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Veröffentlicht in:RNA biology Jg. 14; H. 3; S. 361 - 369
Hauptverfasser: Abdelmohsen, Kotb, Panda, Amaresh C., Munk, Rachel, Grammatikakis, Ioannis, Dudekula, Dawood B., De, Supriyo, Kim, Jiyoung, Noh, Ji Heon, Kim, Kyoung Mi, Martindale, Jennifer L., Gorospe, Myriam
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Taylor & Francis 04.03.2017
Schlagworte:
Base Sequence
Binding Sites
Cell Line, Tumor
Cell proliferation
circPABPN1
circular RNA
ELAV-Like Protein 1 - metabolism
endogenous competing RNA
gene expression
Gene Expression Regulation
human cell lines
human diseases
Humans
HuR
messenger RNA
Models, Biological
neoplasm cells
PABPN1
phenotype
Poly(A)-Binding Protein I - genetics
polyribosomes
Protein Binding
Protein Biosynthesis
Research Paper
RNA - genetics
RNA - metabolism
RNA, Messenger - chemistry
RNA, Messenger - genetics
RNA, Messenger - metabolism
RNA-binding Protein
translation
translation (genetics)
uterine cervical neoplasms
Cell proliferation
HuR
PABPN1
circular RNA
circPABPN1
translation
RNA-binding Protein
endogenous competing RNA
ISSN:1547-6286, 1555-8584, 1555-8584
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Zusammenfassung: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.
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These authors equally contributed to this work.
Supplemental data for this article can be accessed on the publisher's website.
ISSN:1547-6286
1555-8584
1555-8584
DOI:10.1080/15476286.2017.1279788