No abstract

Transfer RNA (tRNA) modification and aminoacylation are post-transcriptional processes that play a crucial role in the function of tRNA and thus represent critical steps in gene expression. Knowledge of the exact processes and effects of the defects in various tRNAs remains incomplete, but a rapidly increasing number of publications over the last decade has shown a growing amount of evidence as to the importance of tRNAs for normal human development, including brain formation and the development and maintenance of higher cognitive functions as well. In this review, we present a synopsis of the literature focusing on tRNA-modifying enzymes and aminoacyl-tRNA synthetases (ARSs) that have been found to be involved in the etiology of hereditary forms of intellectual disability. Our overview shows several parallels but also differences in the symptomatic spectrum observed in individuals affected by intellectual disability caused by mutations in tRNA modifier and/or ARS genes. This observation suggests that tRNAs seem to assume diverse roles in a variety of cellular processes possibly even beyond translation and that not only the abundance but also the modification and aminoacylation levels of tRNAs contribute to cell functions in ways that still remain to be understood.

The full genome of a Methanomassiliicoccales strain, U3.2.1, was obtained from enrichment cultures of percolation fen peat soil under methanogenic conditions, with methanol and hydrogen as the electron acceptor and donor, respectively. Metagenomic assembly of combined long-read and short-read sequences resulted in a 1.51-Mbp circular genome.

While ionizing radiation (IR) is a powerful tool in medical diagnostics, nuclear medicine, and radiology, it also is a serious threat to the integrity of genetic material. Mutagenic effects of IR to the human genome have long been the subject of research, yet still comparatively little is known about the genome-wide effects of IR exposure on the DNA-sequence level. In this study, we employed high throughput sequencing technologies to investigate IR-induced DNA alterations in human gingiva fibroblasts (HGF) that were acutely exposed to 0.5, 2, and 10 Gy of 240 kV X-radiation followed by repair times of 16 h or 7 days before whole-genome sequencing (WGS). Our analysis of the obtained WGS datasets revealed patterns of IR-induced variant (SNV and InDel) accumulation across the genome, within chromosomes as well as around the borders of topologically associating domains (TADs). Chromosome 19 consistently accumulated the highest SNVs and InDels events. Translocations showed variable patterns but with recurrent chromosomes of origin (e.g., Chr7 and Chr16). IR-induced InDels showed a relative increase in number relative to SNVs and a characteristic signature with respect to the frequency of triplet deletions in areas without repetitive or microhomology features. Overall experimental conditions and datasets the majority of SNVs per genome had no or little predicted functional impact with a maximum of 62, showing damaging potential. A dose-dependent effect of IR was surprisingly not apparent. We also observed a significant reduction in transition/transversion (Ti/Tv) ratios for IR-dependent SNVs, which could point to a contribution of the mismatch repair (MMR) system that strongly favors the repair of transitions over transversions, to the IR-induced DNA-damage response in human cells. Taken together, our results show the presence of distinguishable characteristic patterns of IR-induced DNA-alterations on a genome-wide level and implicate DNA-repair mechanisms in the formation of these signatures.