Post-transcriptional control of tumor cell autonomous metastatic potential by the CCR4-NOT deadenylase CNOT7
Accumulating evidence supports the role of an aberrant transcriptome as a driver of metastatic potential. Deadenylation is a general regulatory node for post-transcriptional control by microRNAs and other determinants of RNA stability. Previously, we demonstrated that the CCR4-NOT scaffold component...
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| Format: | Article |
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Public Library of Science
2016
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| Online Access: | https://eprints.nottingham.ac.uk/37556/ |
| _version_ | 1848795483309342720 |
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| author | Faraji, Farhoud Hu, Ying Yang, Howard H. Lee, Maxwell P. Winkler, G. Sebastiaan Hafner, Markus Hunter, Kent W. |
| author_facet | Faraji, Farhoud Hu, Ying Yang, Howard H. Lee, Maxwell P. Winkler, G. Sebastiaan Hafner, Markus Hunter, Kent W. |
| author_sort | Faraji, Farhoud |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Accumulating evidence supports the role of an aberrant transcriptome as a driver of metastatic potential. Deadenylation is a general regulatory node for post-transcriptional control by microRNAs and other determinants of RNA stability. Previously, we demonstrated that the CCR4-NOT scaffold component Cnot2 is an inherited metastasis susceptibility gene. In this study, using orthotopic metastasis assays and genetically engineered mouse models, we show that one of the enzymatic subunits of the CCR4-NOT complex, Cnot7, is also a metastasis modifying gene. We demonstrate that higher expression of Cnot7 drives tumor cell autonomous metastatic potential, which requires its deadenylase activity. Furthermore, metastasis promotion by CNOT7 is dependent on interaction with CNOT1 and TOB1. CNOT7 ribonucleoprotein-immunoprecipitation (RIP) and integrated transcriptome wide analyses reveal that CNOT7-regulated transcripts are enriched for a tripartite 3’UTR motif bound by RNA-binding proteins known to complex with CNOT7, TOB1, and CNOT1. Collectively, our data support a model of CNOT7, TOB1, CNOT1, and RNA-binding proteins collectively exerting post-transcriptional control on a metastasis suppressive transcriptional program to drive tumor cell metastasis. |
| first_indexed | 2025-11-14T19:32:48Z |
| format | Article |
| id | nottingham-37556 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:32:48Z |
| publishDate | 2016 |
| publisher | Public Library of Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-375562020-05-04T17:30:11Z https://eprints.nottingham.ac.uk/37556/ Post-transcriptional control of tumor cell autonomous metastatic potential by the CCR4-NOT deadenylase CNOT7 Faraji, Farhoud Hu, Ying Yang, Howard H. Lee, Maxwell P. Winkler, G. Sebastiaan Hafner, Markus Hunter, Kent W. Accumulating evidence supports the role of an aberrant transcriptome as a driver of metastatic potential. Deadenylation is a general regulatory node for post-transcriptional control by microRNAs and other determinants of RNA stability. Previously, we demonstrated that the CCR4-NOT scaffold component Cnot2 is an inherited metastasis susceptibility gene. In this study, using orthotopic metastasis assays and genetically engineered mouse models, we show that one of the enzymatic subunits of the CCR4-NOT complex, Cnot7, is also a metastasis modifying gene. We demonstrate that higher expression of Cnot7 drives tumor cell autonomous metastatic potential, which requires its deadenylase activity. Furthermore, metastasis promotion by CNOT7 is dependent on interaction with CNOT1 and TOB1. CNOT7 ribonucleoprotein-immunoprecipitation (RIP) and integrated transcriptome wide analyses reveal that CNOT7-regulated transcripts are enriched for a tripartite 3’UTR motif bound by RNA-binding proteins known to complex with CNOT7, TOB1, and CNOT1. Collectively, our data support a model of CNOT7, TOB1, CNOT1, and RNA-binding proteins collectively exerting post-transcriptional control on a metastasis suppressive transcriptional program to drive tumor cell metastasis. Public Library of Science 2016-01-25 Article PeerReviewed Faraji, Farhoud, Hu, Ying, Yang, Howard H., Lee, Maxwell P., Winkler, G. Sebastiaan, Hafner, Markus and Hunter, Kent W. (2016) Post-transcriptional control of tumor cell autonomous metastatic potential by the CCR4-NOT deadenylase CNOT7. PLoS Genetics, 12 . e1005820/1-e1005820/23. ISSN 1553-7404 http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005820 doi:10.1371/journal.pgen.1005820 doi:10.1371/journal.pgen.1005820 |
| spellingShingle | Faraji, Farhoud Hu, Ying Yang, Howard H. Lee, Maxwell P. Winkler, G. Sebastiaan Hafner, Markus Hunter, Kent W. Post-transcriptional control of tumor cell autonomous metastatic potential by the CCR4-NOT deadenylase CNOT7 |
| title | Post-transcriptional control of tumor cell autonomous metastatic potential by the CCR4-NOT deadenylase CNOT7 |
| title_full | Post-transcriptional control of tumor cell autonomous metastatic potential by the CCR4-NOT deadenylase CNOT7 |
| title_fullStr | Post-transcriptional control of tumor cell autonomous metastatic potential by the CCR4-NOT deadenylase CNOT7 |
| title_full_unstemmed | Post-transcriptional control of tumor cell autonomous metastatic potential by the CCR4-NOT deadenylase CNOT7 |
| title_short | Post-transcriptional control of tumor cell autonomous metastatic potential by the CCR4-NOT deadenylase CNOT7 |
| title_sort | post-transcriptional control of tumor cell autonomous metastatic potential by the ccr4-not deadenylase cnot7 |
| url | https://eprints.nottingham.ac.uk/37556/ https://eprints.nottingham.ac.uk/37556/ https://eprints.nottingham.ac.uk/37556/ |