Translation repression via modulation of the cytoplasmic poly(A)-binding protein in the inflammatory response
Gene expression is precisely regulated during the inflammatory response to control infection and limit the detrimental effects of inflammation. Here, we profiled global mRNA translation dynamics in the mouse primary macrophage-mediated inflammatory response and identified hundreds of differentially...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2017-06-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/27786 |
| _version_ | 1828380241935990784 |
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| author | Xu Zhang Xiaoli Chen Qiuying Liu Shaojie Zhang Wenqian Hu |
| author_facet | Xu Zhang Xiaoli Chen Qiuying Liu Shaojie Zhang Wenqian Hu |
| author_sort | Xu Zhang |
| collection | DOAJ |
| description | Gene expression is precisely regulated during the inflammatory response to control infection and limit the detrimental effects of inflammation. Here, we profiled global mRNA translation dynamics in the mouse primary macrophage-mediated inflammatory response and identified hundreds of differentially translated mRNAs. These mRNAs’ 3’UTRs have enriched binding motifs for several RNA-binding proteins, which implies extensive translational regulatory networks. We characterized one such protein, Zfp36, as a translation repressor. Using primary macrophages from a Zfp36-V5 epitope tagged knock-in mouse generated by CRISPR/Cas9-mediated genome editing, we found that the endogenous Zfp36 directly interacts with the cytoplasmic poly(A)-binding protein. Importantly, this interaction is required for the translational repression of Zfp36’s target mRNAs in resolving inflammation. Altogether, these results uncovered critical roles of translational regulations in controlling appropriate gene expression during the inflammatory response and revealed a new biologically relevant molecular mechanism of translational repression via modulating the cytoplasmic poly(A)-binding protein. |
| first_indexed | 2024-12-10T03:54:23Z |
| format | Article |
| id | doaj.art-4185737e90934cce886097de46573f43 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T03:54:23Z |
| publishDate | 2017-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-4185737e90934cce886097de46573f432022-12-22T02:03:10ZengeLife Sciences Publications LtdeLife2050-084X2017-06-01610.7554/eLife.27786Translation repression via modulation of the cytoplasmic poly(A)-binding protein in the inflammatory responseXu Zhang0Xiaoli Chen1Qiuying Liu2Shaojie Zhang3https://orcid.org/0000-0002-4051-5549Wenqian Hu4https://orcid.org/0000-0003-3577-3604Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, United StatesDepartment of Computer Science, University of Central Florida, Orlando, United StatesDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, United StatesDepartment of Computer Science, University of Central Florida, Orlando, United StatesDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, United StatesGene expression is precisely regulated during the inflammatory response to control infection and limit the detrimental effects of inflammation. Here, we profiled global mRNA translation dynamics in the mouse primary macrophage-mediated inflammatory response and identified hundreds of differentially translated mRNAs. These mRNAs’ 3’UTRs have enriched binding motifs for several RNA-binding proteins, which implies extensive translational regulatory networks. We characterized one such protein, Zfp36, as a translation repressor. Using primary macrophages from a Zfp36-V5 epitope tagged knock-in mouse generated by CRISPR/Cas9-mediated genome editing, we found that the endogenous Zfp36 directly interacts with the cytoplasmic poly(A)-binding protein. Importantly, this interaction is required for the translational repression of Zfp36’s target mRNAs in resolving inflammation. Altogether, these results uncovered critical roles of translational regulations in controlling appropriate gene expression during the inflammatory response and revealed a new biologically relevant molecular mechanism of translational repression via modulating the cytoplasmic poly(A)-binding protein.https://elifesciences.org/articles/27786translational controlRNA-binding proteininflammatory responsepost-transcriptional regulationpoly(A) tail binding protein |
| spellingShingle | Xu Zhang Xiaoli Chen Qiuying Liu Shaojie Zhang Wenqian Hu Translation repression via modulation of the cytoplasmic poly(A)-binding protein in the inflammatory response eLife translational control RNA-binding protein inflammatory response post-transcriptional regulation poly(A) tail binding protein |
| title | Translation repression via modulation of the cytoplasmic poly(A)-binding protein in the inflammatory response |
| title_full | Translation repression via modulation of the cytoplasmic poly(A)-binding protein in the inflammatory response |
| title_fullStr | Translation repression via modulation of the cytoplasmic poly(A)-binding protein in the inflammatory response |
| title_full_unstemmed | Translation repression via modulation of the cytoplasmic poly(A)-binding protein in the inflammatory response |
| title_short | Translation repression via modulation of the cytoplasmic poly(A)-binding protein in the inflammatory response |
| title_sort | translation repression via modulation of the cytoplasmic poly a binding protein in the inflammatory response |
| topic | translational control RNA-binding protein inflammatory response post-transcriptional regulation poly(A) tail binding protein |
| url | https://elifesciences.org/articles/27786 |
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