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Enigmatically tRNA genes exist in several hundred copies in mammalian genomes. Here the authors find a precipitous failure of development and increased amino acid misincorporation upon systematic elimination of tRNA-Phe genes in mice using CRISPR.

Here the authors show that loss of TANGO2, a gene linked to an autosomal recessive disorder characterised by developmental delay, rhabdomyolysis, cardiac arrhythmias and metabolic disturbances, disrupts mitochondrial and cytoskeletal structure by impairing its interaction with CRYAB, leading to desmin aggregation and desminopathy, causing cardiomyopathy, muscle weakness, and metabolic dysfunction in mice and human cells.

Lee et al. use three-dimensional cell reconstruction of focused ion beam scanning electron microscopy data and multi-omics to show that ether-lipid metabolism regulates inter-organelle biogenesis and dynamics.

PUF proteins bind RNA sequences through specific interactions between PUF repeats and adenine, guanine and uracil bases. A directed evolution approach has identified new PUF repeats that specifically bind cytosine, which enables the recognition of diverse RNA sequences by engineered PUF proteins.

Iterative computational cycles of mutation and evaluation, modeling the process of directed evolution in silico, enable prediction of mutations that confer nucleic acid-binding activity onto an initial protein with no inherent function.

The ability to alter the genomes of living cells is key to understanding how genes influence the functions of organisms and will be critical to modify living systems for useful purposes. Here, the authors use computational design to discover Cas9 enzymes with increased activity.

Pentatricopeptide repeat (PPR) proteins bind RNA and control diverse aspects of RNA metabolism in eukaryotic cells. Here, Coquille et al.present the crystal structures of several engineered PPR domains, elucidate their RNA binding mode and suggest paths to the design of modular, sequence-specific PPR domains.

Pentatricopeptide repeat proteins bind single-stranded RNA and have been used to study ssRNA biology. Here the authors co-opt these proteins to target ssDNA and demonstrate specific binding of telomere sequences, the structural basis for ssDNA wrapping, and use them as potent telomerase inhibitors.

A directed evolution approach delivers ribosomes with highly functional tethered subunits. Combining the decoding and peptidyl transferase activities of the ribosome into a single entity sets the scene for more efficient protein engineering technologies.

The mitochondrial genome, being compressed to 16 kb, is an attractive model system to investigate how RNA-binding proteins chaperone mRNA lifecycles. Here the authors use RNase footprinting and PAR-CLIP to show that the LRPPRC–SLIRP complex stabilizes mRNA structures to expose sites required for translation and polyadenylation.

Mammalian mitoribosomes feature dramatically reduced ribosomal RNAs and follow mitochondria specific assembly pathways. Here the authors describe the process of human mitochondrial ribosome maturation that results in the formation of the ribosomal active site region, including the peptidyl transferase loop and the two tRNA-binding loops.

Observations from the JWST show the presence of a spectral absorption feature at 4.05 μm arising from SO₂ in the atmosphere of the gas giant exoplanet WASP-39b, which is produced by photochemical processes and verified by numerical models.

A subset of mitochondrial transcripts is not flanked by tRNAs and thus does not conform to the canonical mode of processing. Here, Clemente et al. demonstrate that phosphatase activity of ANGEL2 is required for correct processing of these transcripts.

Rackham and Filipovska review our current understanding of mitochondrial genome organization and expression, and discuss how new technologies and animal models are providing insights into how its mis-regulation leads to diseases of impaired energy conversion.

Mutations in the translational activator of cytochrome c oxidase subunit I (TACO1) causes cytochrome c oxidase deficiency and Leigh Syndrome in patients. Here, the authors characterize mice with a mutation that causes lack of TACO1 expression, identifying a mouse model that could be useful for preclinical trials.

It has been debated whether premature ageing in mitochondrial DNA mutator mice is driven by point mutations or deletions of mtDNA. Matic et al generate Mgme1 knockout mice and show here that these mice have tissue-specific replication stalling and accumulate deleted mtDNA, without developing progeria.

A cryo-electron microscopy structure of the mammalian mitochondrial translation initiation complex reveals unique features that are necessary to initiate mitochondrial translation and highlights a possible membrane-targeting peptide.

Dai et al. show that the transcription factor ATFS-1 interferes with mitochondrial pre-initiation transcription complex assembly and promotes mitochondrial DNA repair, thereby reducing age-dependent mitochondrial DNA damage in Caenorhabditis elegans.

A study from the FANTOM consortium using single-molecule cDNA sequencing of transcription start sites and their usage in human and mouse primary cells, cell lines and tissues reveals insights into the specificity and diversity of transcription patterns across different mammalian cell types.

A low atmospheric carbon abundance can be a ‘habiosignature’ and indicate the presence of substantial surficial liquid water, tectonic activity and/or a biomass in temperate rocky exoplanets. It can potentially be detected by JWST at 4.3 μm in a few tens of transits.

Valik et al. incorporate genomic biomarkers from Pseudomonas aeruginosa isolates and clinical data into machine-learning models to predict the severity of bloodstream infection. Bacterial virulence markers identified through whole genome sequencing offer prognostic insights that could inform treatment strategies in sepsis management.