Transfer RNA-Derived Small RNAs: Another Layer of Gene Regulation and Novel Targets for Disease Therapeutics

초록

Decades after identification as essential for protein synthesis, transfer RNAs (tRNAs) have been implicated in various cellular processes beyond translation. tRNA-derived small RNAs (tsRNAs), referred to as tRNA-derived fragments (tRFs) or tRNA-derived, stress-induced RNAs (tiRNAs), are produced by cleavage at different sites from mature or pre-tRNAs. They are classified into six major types representing potentially thousands of unique sequences and have been implicated to play a wide variety of regulatory roles in maintaining normal homeostasis, cancer cell viability, tumorigenesis, ribosome biogenesis, chromatin remodeling, translational regulation, intergenerational inheritance, retrotransposon regulation, and viral replication. However, the detailed mechanisms governing these processes remain unknown. Aberrant expression of tsRNAs is found in various human disease conditions, suggesting that a further understanding of the regulatory role of tsRNAs will assist in identifying novel biomarkers, potential therapeutic targets, and gene-regulatory tools. Here, we highlight the classification, biogenesis, and biological role of tsRNAs in regulatory mechanisms of normal and disease states. tRNAs can be enzymatically cleaved into different fragments to generate various types of tRNA-derived small RNAs (tsRNAs) that regulate gene expression by various mechanisms that are not well understood. This review describes how tsRNAs are generated and our current understanding of their role(s) in gene regulation in health and disease states. © 2020 The American Society of Gene and Cell Therapy

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