tRFs and tRNA Halves: Novel Cellular Defenders in Multiple Biological Processes

The study of eukaryotic tRNA processing has given rise to an explosion of new information and insights in the last several years. We now have unprecedented knowledge of each step in the tRNA processing pathway, revealing unexpected twists in biochemical pathways, multiple new connections with regulatory pathways, and numerous biological effects of defects in processing steps that have profound consequences throughout eukaryotes, leading to growth phenotypes in the yeast Saccharomyces cerevisiae and to neurological and other disorders in humans. This review highlights seminal new results within the pathways that comprise the life of a tRNA, from its birth after transcription until its death by decay. We focus on new findings and revelations in each step of the pathway including the end-processing and splicing steps, many of the numerous modifications throughout the main body and anticodon loop of tRNA that are so crucial for tRNA function, the intricate tRNA trafficking pathways, and the quality control decay pathways, as well as the biogenesis and biology of tRNA-derived fragments. We also describe the many interactions of these pathways with signaling and other pathways in the cell.

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Products of abortive transcription can prime synthesis of chimeric oligonucleotides

Shavkunov,

Markelova,

Alikina

et al. 2024

Math.Biol.Bioinf.

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The aim of the study was to search for signal RNAs potentially utilized by bacteria for intercellular interactions. This was not limited to a certain category of regulatory RNAs, which are contained in large numbers in all domains of life. The search was performed using RNA-seq data obtained for a wild-type strain of E. coli and its mutant derivative (Δdps) lacking the gene encoding nucleoid protein Dps. This protein can bind RNAs and is found in membrane structures, which indicates the possibility of its participation in their secretion. Since the spectra of intracellular and secreted RNAs differed, it was assumed that the secreted RNAs are somehow selected for secretion. Therefore, in the RNA sets with Dps-dependent secretion, we searched for and found reads with non-template nucleotides at the ends, point nucleotide substitutions, insertions and deletions, as well as regularly detected chimeras. One chimera with a 9-mer GCCAAGGCG at the 5'-end and a transcript from the fimA-fimI intergenic region at the 3'-end was chosen for detailed study. It was found that the 9-mer is a product of abortive transcription from the antisense promoter inside the ravA gene. It is efficiently secreted and forms chimeras with many RNAs, including their 5'-ends and fragments shortened from this terminus. Analysis of the 5'-ends of the 9-mer partners in different chimeras revealed their coding sites in the genome, a feature of which was the ability to form stable secondary structures and therefore cause transcription stops or pauses. The discovery of different chimeras with the 9-mer at the 5'-end witnesses that they are formed as a result of primed synthesis rather than random ligation. The possible biological role of transcription primed by abortive products, whose regulatory role has been established for the first time, is discussed.

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tRFs and tRNA Halves: Novel Cellular Defenders in Multiple Biological Processes

Cited by 3 publications

References 111 publications

Assessing the diagnostic utility of tRNA-derived fragments as biomarkers of head and neck cancer

Assessing the diagnostic utility of tRNA-derived fragments as biomarkers of head and neck cancer

The life and times of a tRNA

Products of abortive transcription can prime synthesis of chimeric oligonucleotides

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