1. Hypoxia and Hypoglycemia synergistically regulate mRNA stability
- Author
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Kristen Carraway, Kyle D. Mansfield, Travis C Kauffmann, Ellen M Johnson, and Nate J. Fry
- Subjects
0301 basic medicine ,Vascular Endothelial Growth Factor A ,medicine.medical_specialty ,RNA Stability ,Ischemia ,chemistry.chemical_element ,RNA-binding protein ,Hypoglycemia ,Oxygen ,03 medical and health sciences ,Heterogeneous-Nuclear Ribonucleoprotein L ,Internal medicine ,medicine ,Humans ,Gene Silencing ,RNA, Messenger ,mRNA stability ,KHSRP ,Hypoxia ,Molecular Biology ,Messenger RNA ,biology ,Osmolar Concentration ,RNA-Binding Proteins ,Cell Biology ,Hypoxia (medical) ,medicine.disease ,Cell Hypoxia ,030104 developmental biology ,Endocrinology ,Glucose ,HEK293 Cells ,chemistry ,CYR61 ,biology.protein ,Trans-Activators ,Mdm2 ,medicine.symptom ,Research Paper - Abstract
Ischemic events, common in many diseases, result from decreased blood flow and impaired delivery of oxygen and glucose to tissues of the body. While much is known about the cellular transcriptional response to ischemia, much less is known about the posttranscriptional response to oxygen and glucose deprivation. The goal of this project was to investigate one such posttranscriptional response, the regulation of mRNA stability. To that end, we have identified several novel ischemia-related mRNAs that are synergistically stabilized by oxygen and glucose deprivation including VEGF, MYC, MDM2, and CYR61. This increase in mRNA half-life requires the synergistic effects of both low oxygen (1%) as well as low glucose (≤ 1 g/L) conditions. Oxygen or glucose deprivation alone fails to initiate the response, as exposure to either high glucose (4 g/L) or normoxic conditions inhibits the response. Furthermore, in response to hypoxia/hypoglycemia, the identified mRNAs are released from the RNA binding protein KHSRP which likely contributes to their stabilization.
- Published
- 2017