title: Hypoxia and Hypoglycemia synergistically regulate mRNA stability.
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.
authors.affiliation: a Biochemistry and Molecular Biology, Brody School of Medicine , East Carolina University , Greenville , NC , USA.
authors.forename: Kristen R
authors.initials: KR
authors.lastname: Carraway
authors.affiliation: a Biochemistry and Molecular Biology, Brody School of Medicine , East Carolina University , Greenville , NC , USA.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Johnson
authors.affiliation: b Brody School of Medicine , East Carolina University , Greenville , NC , USA.
authors.forename: Travis C
authors.identifier: 0000-0003-3197-8194
authors.initials: TC
authors.lastname: Kauffmann
authors.affiliation: a Biochemistry and Molecular Biology, Brody School of Medicine , East Carolina University , Greenville , NC , USA.
authors.forename: Nate J
authors.initials: NJ
authors.lastname: Fry
authors.affiliation: a Biochemistry and Molecular Biology, Brody School of Medicine , East Carolina University , Greenville , NC , USA.
authors.forename: Kyle D
authors.identifier: 0000-0002-5498-9876
authors.initials: KD
authors.lastname: Mansfield
mesh_terms: D015687:Cell Hypoxia / Q000235:genetics; D020868:Gene Silencing; D005947:Glucose / Q000172:deficiency / Q000494:pharmacology; D057809:HEK293 Cells; D034664:Heterogeneous-Nuclear Ribonucleoprotein L / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000235:genetics*; D007511:Ischemia / Q000235:genetics; D009994:Osmolar Concentration; D010100:Oxygen; D020871:RNA Stability / Q000187:drug effects / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D034664:Heterogeneous-Nuclear Ribonucleoprotein L; C105789:KHSRP protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D042461:Vascular Endothelial Growth Factor A; D005947:Glucose; D010100:Oxygen
keywords: Hypoxia; KHSRP; hypoglycemia; mRNA stability