Essential nontranslational functions of tRNA synthetases

Abstract

Nontranslational functions of vertebrate aminoacyl tRNA synthetases (aaRSs), which catalyze the production of aminoacyl-tRNAs for protein synthesis, have recently been discovered. While these new functions were thought to be ‘moonlighting activities’, many are as critical for cellular homeostasis as the activity in translation. New roles have been associated with cytoplasmic forms as well as with nuclear and secreted extracellular forms that impact pathways for cardiovascular development, the immune response, and mTOR, IFN-γ and p53 signaling. The associations of aaRSs with autoimmune disorders, cancers and neurological disorders further highlight nontranslational functions of these proteins. Novel architecture elaborations of the aaRSs accompany their functional expansion in higher organisms and have been associated with the nontranslational functions for several aaRSs. While a general understanding of how these functions developed is limited, the expropriation of aaRSs for essential nontranslational functions may have been initiated by co-opting the amino acid binding site for another purpose.

Upregulation of tryptophanyl-tRNA synthethase adapts human cancer cells to nutritional stress caused by tryptophan degradation

“…The two TrpRS bind tRNAs with different anticodons. WARS2 binds mitochondrial tRNA Trp with the anticodon UCA, which codes for Trp in the mitochondria of humans 40 , while WARS binds cytoplasmic tRNA Trp, which contains the standard anticodon CCA. Little is known about free Trp concentrations in mitochondria and it is therefore not clear how mitochondrial Trp concentrations are affected by Trp depletion.…”

Regulated Capture by Exosomes of mRNAs for Cytoplasmic tRNA Synthetases

“…These domain additions are not needed for catalysis, but rather to endow the synthetases with functions beyond translation. These functions are associated with secreted, extracellular forms and with nuclear forms that are active in many different cell-signaling pathways (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). In addition, a recent study demonstrated that a novel domain, appended to SerRS at the time of the invertebrate to vertebrate transition, was essential for development of the closed vascular system (13).…”

“…In addition, a recent study demonstrated that a novel domain, appended to SerRS at the time of the invertebrate to vertebrate transition, was essential for development of the closed vascular system (13). Thus, novel domains added to tRNA synthetase are endowed with nontranslation functions that are as essential as the activity of the synthetase in protein synthesis (12).…”

Síntese proteica em suínos: como fêmeas, machos não castrados e castrados respondem a este processo?

“…5, Após ser sintetizada, a proteína precisa ser dobrada para atingir sua conformação ativa (adaptado de Lehninger (2006). Na etapa de ativação de AA, que ocorre no citosol, cada um dos 20 AA é covalentemente ligado a um tRNA específico às custas de ATP e enzimas ativadoras dependentes de Mg +2 (aminoacil-tRNA-sintases), tornando o tRNA "carregado" (Monajjemi et al, 2014) sendo, em seguida, transferido para a extremidade 3' do tRNA cognato (Guo & Schimmel, 2013).…”