Hypoxia inducible factor HIF1α elevates expression of mRNA capping enzyme during cobalt chloride-induced hypoxia

Abstract

In response to hypoxia, hypoxia-inducible factors (HIFs) control the transcriptomic output to mitigate the hypoxic stress. Long noncoding RNAs (lncRNA) are found to be very crucial in regulating hypoxia. Like mRNAs, lncRNAs are protected by 5 caps that are added by mRNA capping enzyme (CE) in the nucleus. The previous concept that capping takes place in the nucleus was changed by the recognition of a cytoplasmic pool of capping enzyme (cCE). 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. In this study, we examined the effect of CoCl2 induced hypoxia on cCE and its function in regulating the substrate lncRNAs. Here, we show that CoCl2 induced hypoxia elevates the expressions of nuclear and cytoplasmic CE in HIF1 dependent manner as evidenced by Chromatin immunoprecipitation and HIF1 inhibitor experiments. Furthermore, we found cCE post-transcriptionally controls the stability of its target lncRNAs amidst CoCl2 induced hypoxia. These results suggest that cCE, upregulated by HIF1, may act as a posttranscriptional modulator for a few cCE-targeted lncRNAs.