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Hypoxia-induced gene expression results from selective mRNA partitioning to the endoplasmic reticulum

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Item Type:Article
Title:Hypoxia-induced gene expression results from selective mRNA partitioning to the endoplasmic reticulum
Creators Name:Staudacher, J.J. and Naarmann-de Vries, I.S. and Ujvari, S.J. and Klinger, B. and Kasim, M. and Benko, E. and Ostareck-Lederer, A. and Ostareck, D.H. and Bondke Persson, A. and Lorenzen, S. and Meier, J.C. and Bluethgen, N. and Persson, P.B. and Henrion-Caude, A. and Mrowka, R. and Faehling, M.
Abstract:Protein synthesis is a primary energy-consuming process in the cell. Therefore, under hypoxic conditions, rapid inhibition of global mRNA translation represents a major protective strategy to maintain energy metabolism. How some mRNAs, especially those that encode crucial survival factors, continue to be efficiently translated in hypoxia is not completely understood. By comparing specific transcript levels in ribonucleoprotein complexes, cytoplasmic polysomes and endoplasmic reticulum (ER)-bound ribosomes, we show that the synthesis of proteins encoded by hypoxia marker genes is favoured at the ER in hypoxia. Gene expression profiling revealed that transcripts particularly increased by the HIF-1 transcription factor network show hypoxia-induced enrichment at the ER. We found that mRNAs favourably translated at the ER have higher conservation scores for both the 5'- and 3'-untranslated regions (UTRs) and contain less upstream initiation codons (uAUGs), indicating the significance of these sequence elements for sustained mRNA translation under hypoxic conditions. Furthermore, we found enrichment of specific cis-elements in mRNA 5'- as well as 3'-UTRs that mediate transcript localization to the ER in hypoxia. We conclude that transcriptome partitioning between the cytoplasm and the ER permits selective mRNA translation under conditions of energy shortage.
Keywords:{alpha} Subunit Hypoxia-Inducible Factor 1 , Cell Hypoxia, Cell Line, Cytoplasm, Endoplasmic Reticulum, Gene Expression, Genetic Markers, Initiator Codon, Procollagen-Proline Dioxygenase, Protein Biosynthesis, Protein Disulfide-Isomerases, Messenger RNA, Ribosomes, Transcriptome
Source:Nucleic Acids Research
ISSN:0305-1048
Publisher:Oxford University Press (U.K.)
Volume:43
Number:6
Page Range:3219-3236
Date:31 March 2015
Official Publication:https://doi.org/10.1093/nar/gkv167
PubMed:View item in PubMed

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