Riboswitches are structured non-coding RNAs found in the 5′ UTR of important genes for bacterial metabolism, virulence and survival. Upon the binding of specific ligands that can vary from simple ions to complex molecules such as nucleotides and tRNAs, riboswitches change their local and global mRNA conformations to affect downstream transcription or translation. Due to their dynamic nature and central regulatory role in bacterial metabolism, riboswitches have been exploited as novel RNA-based targets for the development of new generation antibacterials that can overcome drug-resistance problems. During recent years, several important riboswitch structures from many bacterial representatives, including several prominent human pathogens, have shown that riboswitches are ideal RNA targets for new compounds that can interfere with their structure and function, exhibiting much reduced resistance over time. Most interestingly, mainstream antibiotics that target the ribosome have been shown to effectively modulate the regulatory behavior and capacity of several riboswitches, both in vivo and in vitro, emphasizing the need for more in-depth studies and biological evaluation of new antibiotics. Herein, we summarize the currently known compounds that target several main riboswitches and discuss the role of mainstream antibiotics as modulators of T-box riboswitches, in the dawn of an era of novel inhibitors that target important bacterial regulatory RNAs.

The strong decoration of tRNAs with post-transcriptional modifications provides an unprecedented adaptability of this class of non-coding RNAs leading to the regulation of bacterial growth and pathogenicity. Accumulating data indicate that tRNA post-transcriptional modifications possess a central role in both the formation of bacterial cell wall and the modulation of transcription and translation fidelity, but also in the expression of virulence factors. Evolutionary conserved modifications in tRNA nucleosides ensure the proper folding and stability redounding to a totally functional molecule. However, environmental factors including stress conditions can cause various alterations in tRNA modifications, disturbing the pathogen homeostasis. Post-transcriptional modifications adjacent to the anticodon stem-loop, for instance, have been tightly linked to bacterial infectivity. Currently, advances in high throughput methodologies have facilitated the identification and functional investigation of such tRNA modifications offering a broader pool of putative alternative molecular targets and therapeutic avenues against bacterial infections. Herein, we focus on tRNA epitranscriptome shaping regarding modifications with a key role in bacterial infectivity including opportunistic pathogens of the human microbiome.

The mammalian, including the human, postnatal brain harbors distinct neurogenic and oligodendrogenic progenitor populations, whose activity during homeostasis and degeneration is closely related to blood vessels. Here, we investigated the regulatory role of platelets, that are easily and unlimitedly accessible and can modulate tissue regeneration. In co-cultures, platelets created a pro-stemness environment for neural stem/progenitor cells (NSPCs) and enhanced the differentiation of oligodendrocyte progenitor cells. The effects were dependent on platelet numbers and the culture microenvironment, while the molecular signature of the NSPC response confirmed the role of Platelet-Derived Growth Factor and the upregulation of stemness-promoting genes. The same effects were exerted in vivo, but only when platelets were injected directly into the striatal parenchyma or were extravasated, in severely thrombocytopenic mice. In contrast, thrombocytopenia without platelet tissue-infiltration, in Nbeal2 knockout mice, did not affect the brain’s progenitors. Our results, demonstrate the potential value of platelets in neuro-regenerative strategies.

Mitochondrial tRNA genes are critical hotspots for pathogenic mutations and several mitochondrial diseases. They account for approximately 70–75% of disease-causing mtDNA variants despite comprising only 5–10% of the mitochondrial genome. These mutations interfere with mitochondrial translation and affect oxidative phosphorylation, resulting in remarkably heterogeneous multisystem disorders. Under this light, we systematically reviewed PubMed, Scopus, and MITOMAP databases through October 2025, indexing all clinically relevant pathogenic mt-tRNA mutations classified by affected organ systems and underlying molecular mechanisms. Approximately 500 distinct pathogenic variants were identified across all 22 mt-tRNA genes. Beyond typical syndromes like MELAS, MERRF, Leigh syndrome, and Kearns–Sayre syndrome that are linked to mt-tRNA mutations, they increasingly implicate cardiovascular diseases (cardiomyopathy, hypertension), neuromuscular disorders (myopathies, encephalopathies), sensory impairment (hearing loss, optic neuropathy), metabolic dysfunction (diabetes, polycystic ovary syndrome), renal disease, neuropsychiatric conditions, and cancer. Beyond sequence mutations, defects in post-transcriptional modification systems emerge as critical disease mechanisms affecting mt-tRNA function and stability. The mutations on tRNA genes described herein represent potential targets for emerging genome editing therapies, although several translational challenges remain. However, targeted correction of pathogenic mt-tRNA mutations holds transformative potential for precision intervention on mitochondrial diseases.

T-box riboswitches are widespread bacterial regulatory noncoding RNAs that directly interact with tRNAs and switch conformations to regulate the transcription or translation of genes related to amino acid metabolism. Recent studies in Bacilli have revealed the core mechanisms of T-boxes that enable multivalent, specific recognition of both the identity and aminoacylation status of the tRNA substrates. However, in-depth knowledge on a vast number of T-boxes in other bacterial species remains scarce, although a remarkable structural diversity, particularly among pathogens, is apparent. In the present study, analysis of T-boxes that control the transcription of glycyl–tRNA synthetases from four prominent human pathogens revealed significant structural idiosyncrasies. Nonetheless, these diverse T-boxes maintain functional T-box:tRNA^Glyinteractions both in vitro and in vivo. Probing analysis not only validated recent structural observations, but also expanded our knowledge on the substantial diversities among T-boxes and suggest interesting distinctions from the canonical Bacilli T-boxes. Surprisingly, some glycyl T-boxes seem to redirect the T-box trajectory in the absence of recognizable K-turns or contain Stem II modules that are generally absent in glycyl T-boxes. These results consolidate the notion of a lineage-specific diversification and elaboration of the T-box mechanism and corroborate the potential of T-boxes as promising species-specific RNA targets for next-generation antibacterial compounds.

Background/Objectives: The incidence of late-onset sepsis (LOS) has increased with improved survival rates in premature infants. Blood culture, the diagnostic “gold standard”, requires at least 36–72 h for results, leading to empiric antibiotic use and potential resistance. MicroRNAs (miRNAs) have emerged as promising biomarkers for sepsis in adults, but their role in neonatal LOS remains unclear. The aim of this scoping review is to identify the miRNA expression profiles of bacterial LOS in neonates. Methods: A scoping review of the literature was performed between 1 November 2023 and 31 December 2024. Results: Twelve studies fulfilled our criteria and were included in the review. Despite the considerable heterogeneity among the studies, most focused on detecting and quantifying serum microRNAs using real-time PCR, while some examined correlations with other biomarkers, such as CRP. The few microRNAs identified as common across multiple studies showed similar patterns of regulation in LOS cases. Compared to controls (no LOS), neonates with LOS exhibited significant alterations in miRNA expression. More precisely, in LOS, miRNA-181a, miRNA-23b, miRNA-181b5p, miRNA-21-5p, miRNA-34a5p, miRNA-199a3p, miRNA-1184 and miRNA-1295p were downregulated, while miRNA-16, miRNA-146a, miRNA-101, miRNA-187, miRNA-21, miRNA-15a/16 and miRNA-455-5p were upregulated. Conclusions: Currently, there is limited data regarding miRNA expression in LOS. Many studies showed altered expression of specific miRNAs in septic neonates; however, these observations need further validation in larger cohorts and/or randomized controlled trials to confirm their diagnostic potential.