title: Translation arrest and ribonomics in post-ischemic brain: layers and layers of players.
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.
authors.affiliation: Department of Physiology, Wayne State University, Detroit, Michigan, USA. ddegraci@med.wayne.edu
authors.forename: Donald J
authors.initials: DJ
authors.lastname: DeGracia
authors.forename: Jill T
authors.initials: JT
authors.lastname: Jamison
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Szymanski
authors.forename: Monique K
authors.initials: MK
authors.lastname: Lewis
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D015427:Reperfusion Injury / Q000235:genetics* / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D012333:RNA, Messenger