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Background: Although transfer RNA (tRNA) has been found to be the main source of a rich class of noncoding RNA, the tRNA‐derived small RNA (tsRNA) has been proved to play an irreplaceable role in the human body, and its dynamic imbalance could affect the progress of the disease. However, the research on tsRNA in oral submucous fibrosis (OSF) is still scarce. Methods: We sequenced the OSF and validated it by PCR. We found that there were significant differences in their expression levels in OSF. Furthermore, bioinformatic analysis was performed to explore the roles of these fragments in oral submucous fibrosis. Results: Of 126 tsRNAs in OSF were dysregulated, including 73 upregulated tsRNAs and 53 downregulated tsRNAs. The downregulated tiRNA‐Val‐CAC‐002, tRF‐Asn‐GTT‐005, tRF‐Trp‐CCA‐007 and upregulated tRF‐Gly‐TCC‐016, tRF‐Pro‐TGG‐009 showed significant differences by qRT‐PCR validation, which were consistent with the results of RNA sequencing. Gene ontology and pathway analysis revealed that tRF‐Gly‐TCC‐016 would possibly promote the formation and progress of OSF through cytokine‐cytokine receptor interaction and cAMP signal pathway, while tiRNA‐Val‐CAC‐002 could be primarily concerned with the transition from OSF to oral squamous cell carcinoma (OSCC). Conclusion: tRNA‐derived fragments are dysregulated and could be involved in the pathogenesis of oral submucous fibrosis. tRF‐Gly‐TCC‐016 and tiRNA‐Val‐CAC‐002 may be new regulatory molecules that could affect the process of OSF by regulating signal pathways through interacting with multiple genes. [ABSTRACT FROM AUTHOR]

Recent evidence indicates that inhibition of protein translation may be a common pathogenic mechanism for peripheral neuropathy associated with mutant tRNA synthetases (aaRSs). aaRSs are enzymes that ligate amino acids to their cognate tRNA, thus catalyzing the first step of translation. Dominant mutations in five distinct aaRSs cause Charcot-Marie-Tooth (CMT) peripheral neuropathy, characterized by length-dependent degeneration of peripheral motor and sensory axons. Surprisingly, loss of aminoacylation activity is not required for mutant aaRSs to cause CMT. Rather, at least for some mutations, a toxic-gain-of-function mechanism underlies CMT-aaRS. Interestingly, several mutations in two distinct aaRSs were recently shown to inhibit global protein translation in Drosophila models of CMT-aaRS, by a mechanism independent of aminoacylation, suggesting inhibition of translation as a common pathogenic mechanism. Future research aimed at elucidating the molecular mechanisms underlying the translation defect induced by CMT-mutant aaRSs should provide novel insight into the molecular pathogenesis of these incurable diseases. [ABSTRACT FROM AUTHOR]

The maturation of tRNA precursors involves the 5′ cleavage of leader sequences by an essential endonuclease called RNase P. Beyond the ancestral ribonucleoprotein ( RNP) RNase P, a second type of RNase P called PRORP (protein-only RNase P) evolved in eukaryotes. The current view on the distribution of RNase P in cells is that multiple RNPs, multiple PRORPs or a combination of both, perform specialised RNase P activities in the different compartments where gene expression occurs. Here, we identify a single gene encoding PRORP in the green alga Chlamydomonas reinhardtii while no RNP is found. We show that its product, Cr PRORP, is triple-localised to mitochondria, the chloroplast and the nucleus. Its downregulation results in impaired tRNA biogenesis in both organelles and the nucleus. Cr PRORP, as a single-subunit RNase P for an entire organism, makes up the most compact and versatile RNase P machinery described in either prokaryotes or eukaryotes. [ABSTRACT FROM AUTHOR]

Exosomes are secreted nanovesicles that are able to transfer RNA and proteins to target cells. The emerging role of mesenchymal stem cell (MSC) exosomes as promoters of aerobic ATP synthesis restoration in damaged cells, prompted us to assess whether they contain an extramitochondrial aerobic respiration capacity. Exosomes were isolated from culture medium of human MSCs from umbilical cord of =37-wk-old newborns or between 28- to 30-wk-old newborns (i.e., term or preterm infants). Characterization of samples was conducted by cytofluorometry. Oxidative phosphorylation capacity was assessed by Western blot analysis, oximetry, and luminometric and fluorometric analyses. MSC exosomes express functional respiratory complexes I, IV, and V, consuming oxygen. ATP synthesis was only detectable in exosomes from term newborns, suggestive of a specific mechanism that is not completed at an early gestational age. Activities are outward facing and comparable to those detected in mitochondria isolated from term MSCs. MSC exosomes display an unsuspected aerobic respiratory ability independent of whole mitochondria. This may be relevant for their ability to rescue cell bioenergetics. The differential oxidative metabolism of preterm vs. term exosomes sheds new light on the preterm newborn's clinical vulnerability. A reduced ability to repair damaged tissue and an increased capability to cope with anoxic environment for preterm infants can be envisaged. [ABSTRACT FROM AUTHOR]

Endonuclease‐mediated tRNA fragmentation has been observed in many species suggesting functional importance for tRNA fragments. The size distribution of tRNA‐derived fragments indicates the existence of mechanisms that protect tRNAs and their fragments from total degradation by exonucleases. Could post‐transcriptional modifications be important for the controlled processing of tRNAs? [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) is a mitochondrial disease most usually caused by point mutations in tRNA genes encoded by mitochondrial DNA (mtDNA). Approximately 80% of cases of MELAS syndrome are associated with a m.3243A > G mutation in the MT-TL1 gene, which encodes the mitochondrial tRNALeu (UUR). Currently, no effective treatments are available for this chronic progressive disorder. Treatment strategies in MELAS and other mitochondrial diseases consist of several drugs that diminish the deleterious effects of the abnormal respiratory chain function, reduce the presence of toxic agents or correct deficiencies in essential cofactors. EXPERIMENTAL APPROACH We evaluated the effectiveness of some common pharmacological agents that have been utilized in the treatment of MELAS, in yeast, fibroblast and cybrid models of the disease. The yeast model harbouring the A14G mutation in the mitochondrial tRNALeu(UUR) gene, which is equivalent to the A3243G mutation in humans, was used in the initial screening. Next, the most effective drugs that were able to rescue the respiratory deficiency in MELAS yeast mutants were tested in fibroblasts and cybrid models of MELAS disease. KEY RESULTS According to our results, supplementation with riboflavin or coenzyme Q10 effectively reversed the respiratory defect in MELAS yeast and improved the pathologic alterations in MELAS fibroblast and cybrid cell models. CONCLUSIONS AND IMPLICATIONS Our results indicate that cell models have great potential for screening and validating the effects of novel drug candidates for MELAS treatment and presumably also for other diseases with mitochondrial impairment. [ABSTRACT FROM AUTHOR]