Cytoplasmic mRNA capping enzyme is regulated by hypoxia inducible factor HIF1α and controls stability of the target lncRNAs during hypoxia

Abstract

AbstractHypoxia-inducible factors (HIFs) regulate the expression of several hypoxia-responsive RNAs (HRR) to sustain cellular homeostasis. Cytoplasmic pool of mRNA capping enzyme (cCE) has been shown to recap its substrate uncapped mRNAs or long noncoding RNAs (lncRNAs) present in the cytoplasm, preventing their degradation, even during arsenite-induced oxidative stress. Here, we examined the effect of hypoxia on cCE and its function in regulating the substrate lncRNAs. Hypoxia induces expression of cCE in HIF1α dependent manner as evidenced by Chromatin immunoprecipitation and HIF1α inhibitor experiments. Furthermore, we found cCE post-transcriptionally controls the stability of its target lncRNAs amidst hypoxia. These results suggest that cCE may act as a posttranscriptional modulator that could alter the cellular response to hypoxia by stabilizing cCE-targeted lncRNAs.