Metabolic labelling of RNA uncovers the contribution of transcription and decay rates on hypoxia-induced changes in RNA levels.

Metabolic labelling of RNA uncovers the contribution of transcription and decay rates on hypoxia-induced changes in RNA levels. RNA. 2020 Apr 15;: Authors: Tiana M, Acosta-Iborra B, Hernandez-Sierra R, Galiana-Ribote C, Fernandez-Moreno MA, Jimenez B, Del Peso L Abstract Cells adapt to environmental changes, including fluctuations in oxygen levels, through the induction of specific gene expression programs. However, most transcriptomic studies do not distinguish the relative contribution of transcription, RNA processing and RNA degradation processes to cellular homeostasis. Here we used metabolic labeling followed by massive parallel sequencing of newly transcribed and preexisting RNA fractions to simultaneously analyze RNA synthesis and decay in primary endothelial cells exposed to low oxygen tension. We found that changes in transcription rates induced by hypoxia are the major determinant of changes in RNA levels. However, degradation rates also had a significant contribution, accounting for 24% of the observed variability in total mRNA. In addition, our results indicated that hypoxia led to a reduction of the overall mRNA stability from a median half-life in normoxia of 8.7 hours, to 5.7 hours in hypoxia. Analysis of RNA content per cell confirmed a decrease of both mRNA and total RNA in hypoxic samples and that this effect is dependent on the EGLN/HIF/TSC2 axis. This effect could potentially contribute to fundamental global respo...
Source: RNA - Category: Genetics & Stem Cells Authors: Tags: RNA Source Type: research