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Hypoxia or reduced oxygen level is frequently observed in solid tumors. Hypoxia plays a significant role in solid tumor progression and metastasis by stabilizing hypoxia inducible factor (HIF) to activate gene transcription. The majority of human genes are alternatively spliced, producing RNA isoforms that code for functionally distinct proteins. Thus, it is unclear if HIF promotes tumor progression by increasing a particular RNA isoform or all isoforms of each HIF target gene. To address this question, we analyzed hypoxia response at RNA isoform levels [1, 2].

Hypoxia regulates RNA splicing of HIF targets