Ribosome profiling reveals translational regulation of mammalian cells in response to hypoxic stress
Abstract Background Retinal pigment epithelium (RPE) cells transfer oxygen and nutrients from choroid to the neural retina. Reduced oxygen to RPE perturbs development and functions of blood vessels in retina. Previous efforts of genome-wide studies have been largely focused on transcriptional change...
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| Format: | Article |
| Language: | English |
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BMC
2017-08-01
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| Series: | BMC Genomics |
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| Online Access: | http://link.springer.com/article/10.1186/s12864-017-3996-8 |
| _version_ | 1819170624820477952 |
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| author | Zhiwen Jiang Jiaqi Yang Aimei Dai Yuming Wang Wei Li Zhi Xie |
| author_facet | Zhiwen Jiang Jiaqi Yang Aimei Dai Yuming Wang Wei Li Zhi Xie |
| author_sort | Zhiwen Jiang |
| collection | DOAJ |
| description | Abstract Background Retinal pigment epithelium (RPE) cells transfer oxygen and nutrients from choroid to the neural retina. Reduced oxygen to RPE perturbs development and functions of blood vessels in retina. Previous efforts of genome-wide studies have been largely focused on transcriptional changes of cells in response to hypoxia. Recently developed ribosome profiling provides an opportunity to study genome-wide translational changes. To gain systemic insights into the transcriptional and translational regulation of cellular in response to hypoxic stress, we used simultaneous RNA sequencing and ribosome profiling on an RPE cells line, ARPE-19, under hypoxia condition. Results Both HIF-1α and EPAS1 (HIF-2α) proteins were stabilized in ARPE-19 under hypoxic stress treatment at 1 h, 2 h and 4 h. Analysis of simultaneous RNA sequencing and ribosome profiling data showed genome-wide gene expression changes at both transcriptional and translational levels. Comparative analysis of ribosome profiling and RNA-seq data revealed that hypoxia induced changes of more genes at the translational than the transcriptional levels. Ribosomes densities at 5′ untranslated region (UTR) significantly increased under hypoxic stress. Interestingly, the increase in ribosome densities at 5′ UTR is positively correlated with the presence of upstream open reading frames (uORFs) in the 5′ UTR of mRNAs. Conclusion Our results characterized translational profiles of mRNAs for a RPE cell line in response to hypoxia. In particular, uORFs play important roles in the regulation of translation efficiency by affecting ribosomes loading onto mRNAs. This study provides the first attempt to understand translational response of mammalian cells under hypoxic condition. |
| first_indexed | 2024-12-22T19:38:22Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-22T19:38:22Z |
| publishDate | 2017-08-01 |
| publisher | BMC |
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| series | BMC Genomics |
| spelling | doaj.art-fcb09bb6de994c3a8278810084f6e7c72022-12-21T18:14:56ZengBMCBMC Genomics1471-21642017-08-0118111210.1186/s12864-017-3996-8Ribosome profiling reveals translational regulation of mammalian cells in response to hypoxic stressZhiwen Jiang0Jiaqi Yang1Aimei Dai2Yuming Wang3Wei Li4Zhi Xie5State Key Laboratory of Ophthalmology, Guangdong Provincial Key Lab of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Guangdong Provincial Key Lab of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Guangdong Provincial Key Lab of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Guangdong Provincial Key Lab of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityRetinal Neurobiology Section, National Eye InstituteState Key Laboratory of Ophthalmology, Guangdong Provincial Key Lab of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen UniversityAbstract Background Retinal pigment epithelium (RPE) cells transfer oxygen and nutrients from choroid to the neural retina. Reduced oxygen to RPE perturbs development and functions of blood vessels in retina. Previous efforts of genome-wide studies have been largely focused on transcriptional changes of cells in response to hypoxia. Recently developed ribosome profiling provides an opportunity to study genome-wide translational changes. To gain systemic insights into the transcriptional and translational regulation of cellular in response to hypoxic stress, we used simultaneous RNA sequencing and ribosome profiling on an RPE cells line, ARPE-19, under hypoxia condition. Results Both HIF-1α and EPAS1 (HIF-2α) proteins were stabilized in ARPE-19 under hypoxic stress treatment at 1 h, 2 h and 4 h. Analysis of simultaneous RNA sequencing and ribosome profiling data showed genome-wide gene expression changes at both transcriptional and translational levels. Comparative analysis of ribosome profiling and RNA-seq data revealed that hypoxia induced changes of more genes at the translational than the transcriptional levels. Ribosomes densities at 5′ untranslated region (UTR) significantly increased under hypoxic stress. Interestingly, the increase in ribosome densities at 5′ UTR is positively correlated with the presence of upstream open reading frames (uORFs) in the 5′ UTR of mRNAs. Conclusion Our results characterized translational profiles of mRNAs for a RPE cell line in response to hypoxia. In particular, uORFs play important roles in the regulation of translation efficiency by affecting ribosomes loading onto mRNAs. This study provides the first attempt to understand translational response of mammalian cells under hypoxic condition.http://link.springer.com/article/10.1186/s12864-017-3996-8HypoxiaRibosome profilingTranslation efficiencyLoading ratioUpstream open reading frame |
| spellingShingle | Zhiwen Jiang Jiaqi Yang Aimei Dai Yuming Wang Wei Li Zhi Xie Ribosome profiling reveals translational regulation of mammalian cells in response to hypoxic stress BMC Genomics Hypoxia Ribosome profiling Translation efficiency Loading ratio Upstream open reading frame |
| title | Ribosome profiling reveals translational regulation of mammalian cells in response to hypoxic stress |
| title_full | Ribosome profiling reveals translational regulation of mammalian cells in response to hypoxic stress |
| title_fullStr | Ribosome profiling reveals translational regulation of mammalian cells in response to hypoxic stress |
| title_full_unstemmed | Ribosome profiling reveals translational regulation of mammalian cells in response to hypoxic stress |
| title_short | Ribosome profiling reveals translational regulation of mammalian cells in response to hypoxic stress |
| title_sort | ribosome profiling reveals translational regulation of mammalian cells in response to hypoxic stress |
| topic | Hypoxia Ribosome profiling Translation efficiency Loading ratio Upstream open reading frame |
| url | http://link.springer.com/article/10.1186/s12864-017-3996-8 |
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