A stress-responsive RNA switch regulates VEGFA expression

Partho Sarothi Ray, Jie Jia, Peng Yao, Mithu Majumder, Maria Hatzoglou and Paul L. Fox ()
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Partho Sarothi Ray: The Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
Jie Jia: The Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
Peng Yao: The Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
Mithu Majumder: Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA
Maria Hatzoglou: Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA
Paul L. Fox: The Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA

Nature, 2009, vol. 457, issue 7231, 915-919

Abstract: A first human riboswitch RNA switches or riboswitches, involving the binding of small ligands to RNAs, are known to regulate gene expression in bacteria, fungi and plants, where they frequently respond to a deficit or excess of various metabolites or nutrients. Now an RNA switch has been identified in human cells. It is an element in the 3′ untranslated region of the mRNA encoding vascular endothelial growth factor (VEGF), a protein critical for blood vessel formation. The switchable mRNA can bind two different complexes, GAIT or hnRNP L. The binding of one induces a specific conformation that precludes binding of the other. Which factor is bound depends on environmental signals indicating inflammatory and hypoxic status. The switch may have evolved to maintain delivery of oxygen to hypoxic, inflammatory tissues, and may be an example of a type of protein-dependent RNA switch evolved to regulate gene expression in multicellular animals where the precise integration of disparate inputs is more important than a rapid response.

Date: 2009
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DOI: 10.1038/nature07598

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