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Compaction of nucleic acids, namely DNA and RNA, determines their functions and involvement in vital cell processes including transcription, replication, DNA repair and translation. However, experimental probing of the compaction of nucleic acids is not straightforward. In this study, we suggest an approach for this probing using low-frequency Raman spectroscopy. Specifically, we show theoretically, computationally and experimentally the quantifiable correlation between the low-frequency Raman intensity from nucleic acids, magnitude of thermal fluctuations of atomic positions, and the compaction state of biomolecules. Noteworthily, we highlight that the LF Raman intensity differs by an order of magnitude for different samples of DNA, and even for the same sample in the course of long-term storage. The feasibility of the approach is further shown by assessment of the DNA compaction in the nuclei of plant cells. We anticipate that the suggested approach will enlighten compaction of nucleic acids and their dynamics during the key processes of the cell life cycle and under various factors, facilitating advancement of molecular biology and medicine. [ABSTRACT FROM AUTHOR]

Mitochondria carry out various vital roles in eukaryotic cells, including ATP energy synthesis, the regulation of apoptosis, Fe-S cluster formation, and the metabolism of fatty acids, amino acids, and nucleotides. Throughout evolution, mitochondria lost most of their ancestor's genome but kept the replication, transcription, and translation machinery. Protein biosynthesis in mitochondria is specialized in the production of highly hydrophobic proteins encoded by mitochondria. These proteins are components of oxidative phosphorylation chain complexes. The coordination of protein synthesis must be precise to ensure the correct assembly of nuclear-encoded subunits for these complexes. However, the regulatory mechanisms of mitochondrial translation in human cells are not yet fully understood. In this study, we examined the contribution of the SLIRP protein in regulating protein biosynthesis in mitochondria. Using a click-chemistry approach, we discovered that deletion of the SLIRP gene disturbs mitochondrial translation, leading to the dysfunction of complexes I and IV, but it has no significant effect on complexes III and V. We have shown that this protein interacts only with the small subunit of the mitochondrial ribosome, which may indicate its involvement in the regulation of the mitochondrial translation initiation stage. [ABSTRACT FROM AUTHOR]

Parvalbumin‐positive (PV+) fast‐spiking interneurons are essential to control the firing activity of principal neuron ensembles, thereby regulating cognitive processes. The high firing frequency activity of PV+ interneurons imposes high‐energy demands on their metabolism that must be supplied by distinctive machinery for energy generation. Exploring single‐cell transcriptomic data for the mouse cortex, we identified a metabolism‐associated gene with highly restricted expression to PV+ interneurons: Cox6a2, which codes for an isoform of a cytochrome c oxidase subunit. Cox6a2 deletion in mice disrupts perineuronal nets and enhances oxidative stress in PV+ interneurons, which in turn impairs the maturation of their morphological and functional properties. Such dramatic effects were likely due to an essential role of COX6A2 in energy balance of PV+ interneurons, underscored by a decrease in the ATP‐to‐ADP ratio in Cox6a2−/−PV+ interneurons. Energy disbalance and aberrant maturation likely hinder the integration of PV+ interneurons into cortical neuronal circuits, leading to behavioral alterations in mice. Additionally, in a human patient bearing mutations in COX6A2, we found a potential association of the mutations with mental/neurological abnormalities. Synopsis: Whether brain neurons firing at high frequency depend on distinct metabolic machineries to satisfy their increased energy demands remains unclear. Here, combined genetic, functional and behavioural analyses reveal a selective role for the oxidative phosphorylation in stress protection of interneuron by safeguarding their energy supply. Mitochondrial complex IV subunit isoform Cox6a2 is enriched in parvalbumin‐positive (PV+) interneurons in the adult rodent, rhesus monkey, and human brain.PV+ interneuron‐specific Cox6a2 ablation decreases cellular ATP levels and increases oxidative stress in mice.Cox6a2 loss impairs transcriptional and morphological maturation during postnatal stages.Adult Cox6a2‐depleted PV+ interneurons are hyperexcitable and defective in repetitive firing.Cox6a2 depletion results in hyperactivity in vivo. [ABSTRACT FROM AUTHOR]

RNA molecules of all species contain modified nucleotides and particularly m5U residues. The vertebrate mitochondrial small subunit rRNA contains m5U nucleotide in a unique site. In this work we found an enzyme, TRMT2B, responsible for the formation of this nucleotide and m5U residues in a number of mitochondrial tRNA species. Inactivation of the Trmt2B gene leads to a reduction of the activity of respiratory chain complexes I, III and IV, containing the subunits synthesized by the mitochondrial protein synthesis apparatus. Comparative sequence analysis of m5U-specific RNA methyltransferases revealed an unusual evolutionary pathway of TRMT2B formation which includes consecutive substrate specificity switches from the large subunit rRNA to tRNA and then to the small subunit rRNA. [ABSTRACT FROM AUTHOR]

A glycolytic enzyme, enolase, is identified as a factor of tRK1 import in Saccharomyces cerevisiae and the recombination enolase and preMSK1p which are sufficient to direct RNA import in vitro is demonstrated and depletion of enolase inhibits tRNA import in vivo. A model suggesting that the cell exploits mitochonrial targeting of the enolase in order to address the tRNA toward peri-mitochondrically synthesized preMsk1p is proposed.

After billions of years of evolution, mitochondrion retains its own genome, which gets expressed in mitochondrial matrix. Mitochondrial translation machinery rather differs from modern bacterial and eukaryotic cytosolic systems. Any disturbance in mitochondrial translation drastically impairs mitochondrial function. In budding yeast Saccharomyces cerevisiae, deletion of the gene coding for mitochondrial translation initiation factor 3—AIM23, leads to an imbalance in mitochondrial protein synthesis and significantly delays growth after shifting from fermentable to non-fermentable carbon sources. Molecular mechanism underlying this adaptation to respiratory growth was unknown. Here, we demonstrate that slow adaptation from glycolysis to respiration in the absence of Aim23p is accompanied by a gradual increase of cytochrome c oxidase activity and by increased levels of Tma19p protein, which protects mitochondria from oxidative stress. [ABSTRACT FROM AUTHOR]

RNA molecules of all species contain modified nucleotides and particularly m 5 U residues. The vertebrate mitochondrial small subunit rRNA contains m 5 U nucleotide in a unique site. In this work we found an enzyme, TRMT2B, responsible for the formation of this nucleotide and m 5 U residues in a number of mitochondrial tRNA species. Inactivation of the Trmt2B gene leads to a reduction of the activity of respiratory chain complexes I, III and IV, containing the subunits synthesized by the mitochondrial protein synthesis apparatus. Comparative sequence analysis of m 5 U-specific RNA methyltransferases revealed an unusual evolutionary pathway of TRMT2B formation which includes consecutive substrate specificity switches from the large subunit rRNA to tRNA and then to the small subunit rRNA.