Ribonucleosides from tRNA in Hyperglycemic Mammalian Cells and Diabetic Murine Cardiac Models Article (Faculty180)

cited authors

  • Dodson, Taylor A; Nieuwoud, Stephen; Morse, Chase N; Liu, Chao; Pierre, Valinteshley; Senyo, Samuel E; Prestwich, Erin G


  • <p><span style="font-size:7pt;font-style:italic;">Aims: </span><span style="font-size:7pt;">Cardiomyopathy is a diabetic comorbidity with few molecular targets. To address this, we evaluated transfer RNA (tRNA) modifications in the diabetic heart because tRNA modifications have been implicated in diabetic etiologies.<br></span><span style="font-size:7pt;font-style:italic;">Main methods: </span><span style="font-size:7pt;">tRNA was isolated from aorta, apex, and atrial tissue of healthy and diabetic murine hearts and related hyperglycemic cell models. tRNA modifications and canonical ribonucleosides were quantified by liquid- chromatography tandem mass spectrometry (LC-MS/MS) using stable isotope dilution. Correlations between ribonucleosides and diabetic comorbidity pathology were assessed using statistical analyses. </span></p> <p><span style="font-size:7pt;font-style:italic;">Key findings: </span><span style="font-size:7pt;">Total tRNA ribonucleoside levels were analyzed from cell types and healthy and diabetic murine heart tissue. Each heart structure had characteristic ribonucleoside profiles and quantities. Several ribonucleo- sides were observed as significantly different in hyperglycemic cells and diabetic tissues. In hyperglycemic models, ribonucleosides N</span><span style="font-size:5pt;">4</span><span style="font-size:7pt;">-acetylcytidine (ac</span><span style="font-size:5pt;">4</span><span style="font-size:7pt;">C), 5-methoxycarbonylmethyl-2-thiouridine (mcm</span><span style="font-size:5pt;">5</span><span style="font-size:7pt;">s</span><span style="font-size:5pt;">2</span><span style="font-size:7pt;">U), 5-meth- ylcytidine (m</span><span style="font-size:5pt;">5</span><span style="font-size:7pt;">C), and N</span><span style="font-size:5pt;">1</span><span style="font-size:7pt;">-methylguanosine (m</span><span style="font-size:5pt;">1</span><span style="font-size:7pt;">G) were anomalous. Specific tRNA modifications known to be on murine tRNA</span><span style="font-size:5pt;">Ini(CAU) </span><span style="font-size:7pt;">were higher in diabetic heart tissue which suggests that tRNA modifications could be regulating translation in diabetes. </span></p> <p><span style="font-size:7pt;font-style:italic;">Significance: </span><span style="font-size:7pt;">We identified tRNA ribonucleosides and tRNA species associated with hyperglycemia and diabetic etiology. </span></p>

publication date

  • 2023

published in