Regulation of mRNA following brain ischemia and reperfusion

• Published in: Wiley interdisciplinary reviews. RNA 2017-07, Vol.8 (4), p.e1415-n/a
• Main Author: DeGracia, Donald J.
• Format: Article
• Language: English
• Subjects: Animals; Brain Ischemia - genetics; Brain Ischemia - metabolism; Cell death; Cerebral blood flow; Gene Expression Regulation; Heart; Heart diseases; Heat shock proteins; Humans; Ischemia; Metabolic networks; mRNA; Neurons - metabolism; Neurons - pathology; Neuroprotection; Protein Biosynthesis - genetics; Reperfusion; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stroke
• ISSN: 1757-7004; 1757-7012
• DOI: 10.1002/wrna.1415

There is growing appreciation that mRNA regulation plays important roles in disease and injury. mRNA regulation and ribonomics occur in brain ischemia and reperfusion (I/R) following stroke and cardiac arrest and resuscitation. It was recognized over 40 years ago that translation arrest (TA) accompanies brain I/R and is now recognized as part of the intrinsic stress responses triggered in neurons. However, neuron death correlates to a prolonged TA in cells fated to undergo delayed neuronal death (DND). Dysfunction of mRNA regulatory processes in cells fated to DND prevents them from translating stress‐induced mRNAs such as heat shock proteins. The morphological and biochemical studies of mRNA regulation in postischemic neurons are discussed in the context of the large variety of molecular damage induced by ischemic injury. Open issues and areas of future investigation are highlighted. A sober look at the molecular complexity of ischemia‐induced neuronal injury suggests that a network framework will assist in making sense of this complexity. The ribonomic network sits between the gene network and the various protein and metabolic networks. Thus, targeting the ribonomic network may prove more effective at neuroprotection than targeting specific molecular pathways, for which all efforts have failed to the present time to stop DND in stroke and after cardiac arrest. WIREs RNA 2017, 8:e1415. doi: 10.1002/wrna.1415 This article is categorized under: RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems RNA Evolution and Genomics > Ribonomics RNA in Disease and Development > RNA in Disease Dramatic image of CA3 neuron after 10‐min brain ischemia and 1‐h reperfusion shows redistribution of HuR (red) and polyadenylated mRNAs (green).