Deep analysis of next-generation sequencing data unveils numerous small non-coding RNAs with distinct functions. Recently, fragments derived from tRNA, named as tRNA-derived small RNA (tsRNA), have attracted broad attention. There are mainly two types of tsRNAs, including tRNA-derived stress-induced RNA (tiRNA) and tRNA-derived fragment (tRF), which differ in the cleavage position of the precursor or mature tRNA transcript. Emerging evidence has shown that tsRNAs are not merely tRNA degradation debris but have been recognized to play regulatory roles in many specific physiological and pathological processes. In this review, we summarize the biogeneses of various tsRNAs, present the emerging concepts regarding functions and mechanisms of action of tsRNAs, highlight the potential application of tsRNAs in human diseases, and put forward the current problems and future research directions.

tRNA-Derived Small RNA: A Novel Regulatory Small Non-Coding RNA

As the adaptor that decodes mRNA sequence into protein, the basic aspects of tRNA structure and function are central to all studies of biology. Yet the complexities of their properties and cellular roles go beyond the view of tRNAs as static participants in protein synthesis. Detailed analyses through more than 60 years of study have revealed tRNAs to be a fascinatingly diverse group of molecules in form and function, impacting cell biology, physiology, disease and synthetic biology. This review analyzes tRNA structure, biosynthesis and function, and includes topics that demonstrate their diversity and growing importance.

https://www.tandfonline.com/doi/pdf/10.1080/15476286.2020.1809197

Transfer RNAs: diversity in form and function.

Pathological significance of tRNA-derived small RNAs in neurological disorders

Transfer RNAs (tRNAs) are essential for protein synthesis. Mature or pre-tRNAs may be cleaved to produce tRNA-derived small RNAs (tsRNAs). tsRNAs, divided into tRNA-derived stress-induced RNA (tiRNAs) and tRNA-derived fragments (tRFs), play versatile roles in a number of fundamental biological processes. tsRNAs not only play regulatory roles in gene silencing, RNA stability, reverse transcription, and translation, but are also closely related to cell proliferation, migration, cell cycle, and apoptosis. Their abnormal expression is associated with the occurrence and development of various human diseases, especially cancer. This paper reviews the classification, biogenesis, and mechanism of action of tsRNAs, and the research progress to date on tsRNAs in cancers. These findings provide new opportunities for diagnostic biomarkers and treatment targets of several types of cancers including gastric cancer, colorectal cancer, hepatocellular carcinomas, pancreatic cancer, breast cancer, prostate cancer, renal cell carcinoma, ovarian cancer, lung cancer, bladder cancer, thyroid cancer, oral cancer, and leukemia. 

https://doi.org/10.1016/j.gendis.2021.12.009

tRNA-derived small RNAs: Mechanisms and potential roles in cancers

BackgroundAggregation of malformed proteins is a key feature of many neurodegenerative diseases, but the mechanisms that drive proteinopathy in the brain are poorly understood. We aimed to characterize aggregated proteins in human brain tissues affected by dementia.ResultsTo characterize amyloidal plaque purified from post-mortem brain tissue of dementia patient, we applied ultracentrifugation-electrostatic repulsion hydrophilic interaction chromatography (UC-ERLIC) coupled mass spectrometry-based proteomics technologies. Proteomics profiling of both soluble and aggregated amyloidal plaque demonstrated significant enrichment and deamidation of S100A9, ferritin, hemoglobin subunits, creatine kinase and collagen protein among the aggregated brain proteins. Amyloidal plaques were enriched in the deamidated variant of protein S100A9, and structural analysis indicated that both the low- and high-affinity calcium binding motifs of S100A9 were deamidated exclusively in the aggregated fraction, suggesting altered charge state and function of this protein in brain tissues affected by dementia. The multiple deamidated residues of S100A9 predicts introduction of negative charge that alter Ca++ binding, suggesting increased capacity to form pathological aggregates in the brain.ConclusionUC-coupled proteomics revealed that brain amyloidal plaques are enriched in deamidated proteins, and suggested that altered charge state and calcium-binding capacity of S100A9 may enhance protein aggregation and promote neurodegeneration in the human brain.

Additional file 1: Table S1A. of Dementia-linked amyloidosis is associated with brain protein deamidation as revealed by proteomic profiling of human brain tissues

Transfer RNA (tRNA)-derived small RNAs (tsRNAs) have recently emerged as important regulators of protein translation and shown to have diverse biological functions. However, the underlying cellular and molecular mechanisms of tsRNA function in the context of dynamic cell-state transitions remain unclear. Here we report the identification of a set of tsRNAs upregulated in differentiating mouse embryonic stem cells (mESCs). Mechanistic analyses revealed primary functions of tsRNAs in regulating polysome assembly and translation. Notably, interactome studies with differentially-enriched tsRNAs revealed a switch in associations with 9effector9 RNPs and 9target9 mRNAs in different cell-states. We also demonstrate that a specific pool of tsRNAs can interact with Igf2bp1, an RNA-binding protein, to influence the expression of the pluripotency-promoting factor-c-Myc, thereby providing evidence for tsRNAs in modulating stem cell-states in mESCs. Finally, tsRNA expression analyses in distinct, heterologous cell and tissue models of stem/transformed versus differentiated/normal states reveal that tsRNA-mediated regulation of protein translation may represent a global biological phenomenon associated with cell-state transitions.

https://www.biorxiv.org/content/biorxiv/early/2017/07/01/158501.full.pdf

Dynamic expression of tRNA-derived small RNAs define cellular states

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Dynamic expression of tRNA-derived small RNAs define cellular states