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tRNAs are the central adaptor molecule in translation and require a wide variety of post-transcriptional modifications to fulfill their functions. The model gram-negative K-12 is one of the handfuls of bacteria where all the tRNA modifications and corresponding genes have been characterized. This work dissects epistatic relationships between tRNA modification genes in by conducting a synthetic lethal screen revealing 5 pairs of modifications that cannot be deleted in combination when cells are grown in rich media, and 15 pairs of modifications that lead to growth defects when deleted in combination. The gene involved in the insertion of Psi residues at positions 38 to 40 in multiple tRNAs gave the highest number of synthetic lethality phenotypes that could be complemented by the expression of the gene and in some cases suppressed by the overexpression of target tRNAs. A pilot phenotype screen of strains lacking two tRNA modifications genes viable in rich media lead to the identification of growth conditions that exhibited poor growth. This work lays the foundation to dissect the role of modifications in tRNA quality control.
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http://dx.doi.org/10.1101/2024.11.12.622971 | DOI Listing |
Front Cardiovasc Med
August 2025
The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, Jiangxi, China.
tRNA-derived small RNAs (tsRNAs) are a class of non-coding RNAs that are generated by cleavage of precursors or mature tRNAs under stress conditions such as hypoxia, oxidative stress and nutrient deficiency. Recent breakthroughs in RNA sequencing technology have revealed their association with cardiovascular diseases (CVDs), including myocardial infarction (MI), atherosclerosis, cardiac hypertrophy, aortic coarctation, and pulmonary arterial hypertension. tsRNAs play important biological functions in these diseases, including the inhibition of apoptosis, epigenetic modification, intercellular signaling mediation, translation, and regulation of gene expression.
View Article and Find Full Text PDFJ Biol Chem
September 2025
Department of Chemistry and Center for Molecular Signaling, Wake Forest University, Winston-Salem, NC, 27109. Electronic address:
The AUA isoleucine codon is generally rare and used with varying frequency in bacterial genomes. The tRNA responsible for decoding this trinucleotide must be modified at the wobble position by tRNA lysidine synthetase (TilS) prior to aminoacylation and accommodation at the ribosome. To test the hypothesis that TilS catalytic efficiency correlates with AUA frequency, we cloned tilS genes from bacteria with varying AUA codon usage.
View Article and Find Full Text PDFRibosomal RNA (rRNA) modifications are important for ribosome function and can influence bacterial susceptibility to ribosome-targeting antibiotics. The universally conserved 16S rRNA nucleotide C1402, for example, is the only 2'- -methylated nucleotide in the bacterial small (30S) ribosomal subunit and this modification fine tunes the shape and structure of the peptidyl tRNA binding site. The Cm1402 modification is incorporated by the conserved bacterial 16S rRNA methyltransferase RsmI, but it is unclear how RsmI is able to recognize its 30S substrate and specifically modify its buried target nucleotide.
View Article and Find Full Text PDFMetastasis is the leading cause of cancer related deaths, however therapies specifically targeting metastasis are lacking and remain a dire therapeutic need in the clinic. Metastasis is a highly inefficient process that is inhibited by extracellular stress. Therefore, metastasizing cells that ultimately survive and successfully colonize distant organs must undergo molecular rewiring to mitigate stress.
View Article and Find Full Text PDFArtemisinin has long been a first-line antimalarial. Yet, its mode of action is still poorly understood. Emergence of artemisinin-resistant strains highlight the importance of addressing this question so as to develop better drugs and overcome resistance.
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