Translation arrest and ribonomics in post-ischemic brain: Layers and layers of players

Donald J. DeGracia, Jill T. Jamison, Jeffrey J. Szymanski, Monique K. Lewis

Research output: Contribution to journalReview articlepeer-review

43 Scopus citations

Abstract

A persistent translation arrest (TA) correlates precisely with the selective vulnerability of post-ischemic neurons. Mechanisms of post-ischemic TA that have been assessed include ribosome biochemistry, the link between TA and stress responses, and the inactivation of translational components via sequestration in subcellular structures. Each of these approaches provides a perspective on post-ischemic TA. Here, we develop the notion that mRNA regulation via RNA-binding proteins, or ribonomics, also contributes to post-ischemic TA. We describe the ribonomic network, or structures involved in mRNA regulation, including nuclear foci, polysomes, stress granules, embryonic lethal abnormal vision/Hu granules, processing bodies, exosomes, and RNA granules. Transcriptional, ribonomic, and ribosomal regulation together provide multiple layers mediating cell reprogramming. Stress gene induction via the heat-shock response, immediate early genes, and endoplasmic reticulum stress represents significant reprogramming of post-ischemic neurons. We present a model of post-ischemic TA in ischemia-resistant neurons that incorporates ribonomic considerations. In this model, selective translation of stress-induced mRNAs contributes to translation recovery. This model provides a basis to study dysfunctional stress responses in vulnerable neurons, with a key focus on the inability of vulnerable neurons to selectively translate stress-induced mRNAs. We suggest a ribonomic approach will shed new light on the roles of mRNA regulation in persistent TA in vulnerable post-ischemic neurons.

Original languageEnglish
Pages (from-to)2288-2301
Number of pages14
JournalJournal of Neurochemistry
Volume106
Issue number6
DOIs
StatePublished - Sep 2008

Keywords

  • Brain ischemia and reperfusion
  • Heat shock response
  • Protein synthesis inhibition
  • RNA operons
  • Stress granules
  • Translation arrest

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