Ribosome profiling reveals translational regulation of mammalian cells in response to hypoxic stress

BMC Genomics

Research Article

Wei Li¹  Zhiwen Jiang²  Jiaqi Yang²  Yuming Wang²  Aimei Dai²  Zhi Xie² 

[1] Retinal Neurobiology Section, National Eye Institute, Bethesda, MD, USA;State Key Laboratory of Ophthalmology, Guangdong Provincial Key Lab of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China;

关键词: Hypoxia;    Ribosome profiling;    Translation efficiency;    Loading ratio;    Upstream open reading frame;   

DOI  :  10.1186/s12864-017-3996-8

 received in 2017-01-04, accepted in 2017-08-01,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundRetinal 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.ResultsBoth 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.ConclusionOur 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.

【 授权许可】

CC BY   
© The Author(s). 2017