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

Nucleic Acids Research
Jonas J StaudacherMichael Fähling

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 tran...Continue Reading

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Citations

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Jun 29, 2021·Frontiers in Molecular Biosciences·Sebastian de VriesAntje Ostareck-Lederer

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Datasets Mentioned

BETA
GSE49029
GM130

Methods Mentioned

BETA
PCR
transfection

Software Mentioned

DREME ( Discriminative Regular Expression Motif Elicitation
R
ImageJ
GEne SeT AnaLysis Toolkit
Biomart
Rcmdr
DREME
MEME
WebGestalt

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