Correction: Entamoeba lysyl-tRNA Synthetase Contains a Cytokine-Like Domain with Chemokine Activity towards Human Endothelial Cells.

[This corrects the article DOI: 10.1371/journal.pntd.0001398.].

Decreased expression of mitochondrial aminoacyl-tRNA synthetases causes downregulation of OXPHOS subunits in type 2 diabetic muscle.

Type 2 diabetes mellitus (T2D) affects millions of people worldwide and is one of the leading causes of morbidity and mortality. The skeletal muscle (SKM) is one of the most important tissues involved in maintaining glucose homeostasis and substrate oxidation, and it undergoes insulin resistance in T2D. In this study, we identify the existence of alterations in the expression of mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) in skeletal muscle from two different forms of T2D: early-onset type 2 diabetes (YT2) (onset of the disease before 30 years of age) and the classical form of the disease (OT2). GSEA analysis from microarray studies revealed the repression of mitochondrial mt-aaRSs independently of age, which was validated by real-time PCR assays. In agreement with this, a reduced expression of several encoding mt-aaRSs was also detected in skeletal muscle from diabetic (db/db) mice but not in obese ob/ob mice. In addition, the expression of the mt-aaRSs proteins most relevant in the synthesis of mitochondrial proteins, threonyl-tRNA, and leucyl-tRNA synthetases (TARS2 and LARS2) were also repressed in muscle from db/db mice. It is likely that these alterations participate in the reduced expression of proteins synthesized in the mitochondria detected in db/db mice. We also document an increased iNOS abundance in mitochondrial-enriched muscle fractions from diabetic mice that may inhibit aminoacylation of TARS2 and LARS2 by nitrosative stress. Our results indicate a reduced expression of mt-aaRSs in skeletal muscle from T2D patients, which may participate in the reduced expression of proteins synthesized in mitochondria. An enhanced mitochondrial iNOS could play a regulatory role in diabetes.

Loss of the tRNALysCUU encoding gene, Chr-11 tRNA-Lys-CUU, is not associated with Type 2 diabetes mellitus.

AIM: To investigate the presence/absence of the Chr-11 tRNA-Lys-CUU gene as a marker for genetic predisposition to Type 2 diabetes mellitus (T2DM). METHODS: We enrolled 122 patients diagnosed with T2DM and 77 non-diabetic individuals. We evaluated clinical and biochemical parameters (body mass index, hypertension, cholesterol levels, glycosylated hemoglobin, triglycerides, etc.), and performed a genotypic profiling of Chr-11 tRNA-Lys-CUU by polymerase chain reaction analyses. RESULTS: Approximately one third of the population lacked Chr-11 tRNA-Lys-CUU. We did not observe a statistically significant association between the presence/absence of Chr-11 tRNA-Lys-CUU and T2DM. CONCLUSION: The genotypic distribution of Chr-11 tRNA-Lys-CUU in our population was consistent to that reported by others. This gene failed as a marker for T2DM predisposition.

tRNA Methyltransferase Defects and Intellectual Disability.

In all organisms, transfer RNA (tRNA) molecules are required to undergo post-transcriptional modifications at different levels in order to convert into mature tRNAs. These modifications are critical for many aspects of tRNA function and structure, such as translational efficiency, flexibility, codon-anticodon interaction, stability, and fidelity. Up to now, over 100 modified nucleosides have been identified in tRNAs from all domains of life. Post-transcriptional modifications include different chemical processes such as methylation, deamination, or acetylation, with methylation reactions as the most common. tRNA methyltransferases are a family of enzymes involved in the post-transcriptional methylation of tRNA bases. Recent studies have reported different human diseases resulting from defects in tRNA methyltransferase activity, including cancer, diabetes and neurological disorders such as intellectual disability (ID). In this article, we focused on biological function and characterization of tRNA methyltransferases associated with ID in order to explain how functional disruption of tRNA methyltransferases could lead to ID phenotype.