Vascular endothelial growth factor-A (VEGFA) has been shown to reduce apoptosis under hypoxic stress. However, its regulation was not previously understood. In this paper, they show that interferon-γ (IFN-γ) represses the expression of VEGFA, whereas heterogeneous nuclear ribonucleoprotein L (HNRNPL) allows translation to occur. This turning on and off of transcription, they found, was due to these proteins binding to VEGFA’s 5’ UTR which is called the hypoxia stability region (HSR).
This RNA switch is not like the classic riboswitch that regulates gene expression in the presence of a small molecule. However, it still does regulate gene expression by undergoing conformational changes in response to environmental signals. It is the first of its kind found in mamialian cells, but the author believes more still be present.
As an interesting note, this switch seems to be only active in myeloid cells and not the universally used HeLa cells.
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