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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| Vydáno v: | RNA biology Ročník 14; číslo 3; s. 361 - 369 |
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| Hlavní autoři: | , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
United States
Taylor & Francis
04.03.2017
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| Témata: | |
| ISSN: | 1547-6286, 1555-8584, 1555-8584 |
| On-line přístup: | Získat plný text |
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| 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. |
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| AbstractList | 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. 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.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. |
| Author | Abdelmohsen, Kotb Panda, Amaresh C. Noh, Ji Heon Kim, Kyoung Mi Gorospe, Myriam Grammatikakis, Ioannis Dudekula, Dawood B. De, Supriyo Kim, Jiyoung Martindale, Jennifer L. Munk, Rachel |
| Author_xml | – sequence: 1 givenname: Kotb surname: Abdelmohsen fullname: Abdelmohsen, Kotb email: abdelmohsenk@mail.nih.gov, abdelmohsenk@grc.nia.nih.gov organization: Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health – sequence: 2 givenname: Amaresh C. surname: Panda fullname: Panda, Amaresh C. organization: Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health – sequence: 3 givenname: Rachel surname: Munk fullname: Munk, Rachel organization: Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health – sequence: 4 givenname: Ioannis surname: Grammatikakis fullname: Grammatikakis, Ioannis organization: Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health – sequence: 5 givenname: Dawood B. surname: Dudekula fullname: Dudekula, Dawood B. organization: Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health – sequence: 6 givenname: Supriyo surname: De fullname: De, Supriyo organization: Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health – sequence: 7 givenname: Jiyoung surname: Kim fullname: Kim, Jiyoung organization: Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health – sequence: 8 givenname: Ji Heon surname: Noh fullname: Noh, Ji Heon organization: Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health – sequence: 9 givenname: Kyoung Mi surname: Kim fullname: Kim, Kyoung Mi organization: Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health – sequence: 10 givenname: Jennifer L. surname: Martindale fullname: Martindale, Jennifer L. organization: Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health – sequence: 11 givenname: Myriam surname: Gorospe fullname: Gorospe, Myriam organization: Laboratory of Genetics and Genomics, National Institute on Aging, National Institutes of Health |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28080204$$D View this record in MEDLINE/PubMed |
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| Snippet | HuR influences gene expression programs and hence cellular phenotypes by binding to hundreds of coding and noncoding linear RNAs. However, whether HuR binds to... |
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| SubjectTerms | 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 |
| Title | Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1 |
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