title: tRNA fragmentation and protein translation dynamics in the course of kidney injury.
abstract: Cells under stressful microenvironmental conditions initiate integrated molecular circuitries that aim at reducing general protein translation rates while redirecting protein synthesis toward a selective set of stress-response proteins. The consequence of the activation of this dynamic system is a reduction of the energy expenditure of the cell, and a metabolic rewiring that shapes adaptation under stress, which will, in fine, promote cell survival. In general, the translation initiation step is the prime target of translation reduction, with 2 molcular modules inhibiting translation initiation: the mechanistic target of Rapamycin complex 1, and the stress related kinases eIF2 kinases, which are all involved in the cellular responses to kidney injuries. tRNA (tRNA) dynamics and fragmentation have recently gained a considerable weight in the field of the non-coding RNA biology, and emerge as an important system for protein translation modulation under cellular stress. More precisely, stress-induced tRNA (tiRNA), the cleavage products of the ribonuclease angiogenin, are generated under various stress conditions, including oxidative stress and endoplasmic reticulum stress, and contribute to protein translation reprogramming in mammal cells. Current clinical and experimental evidence indicates that the angiogenin-tRNA fragmentation system is initiated under renal insults, and is involved in the tissue adaptation upon kidney injury. In addition, this system represents a potential source for minimally-invasive or non invasive biomarkers of early kidney injury. Besides RNA interference, tRNA fragments are likely involved in other fundamental cellular functions, including inflammation, and a better understanding of the molecular basis of tRNA functions will drive discoveries on the fundamental role of non coding RNA biology, as exemplified by microRNA, in the regulation of kidney homeostasis.
authors.affiliation: a INSERM U1147, Center Universitaire des Saints Pères , Paris , France.|b Université Paris Descartes , Paris , France.
authors.forename: Iadh
authors.initials: I
authors.lastname: Mami
authors.affiliation: a INSERM U1147, Center Universitaire des Saints Pères , Paris , France.|b Université Paris Descartes , Paris , France.|c Service de Biochimie, Hôpital Européen Gorges Pompidou , Paris , France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pallet
mesh_terms: D000818:Animals; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D007511:Ischemia / Q000235:genetics; D007668:Kidney / Q000098:blood supply / Q000502:physiology / Q000503:physiopathology*; D007674:Kidney Diseases / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress; D014176:Protein Biosynthesis; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism*; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D012343:RNA, Transfer; C046366:angiogenin; D012259:Ribonuclease, Pancreatic
keywords: Acute kidney injury; endoplasmic reticulum stress; tiRNA; transfer RNA; unfolded protein response