Emerging roles of tRNA-derived small RNAs in cancer biology

Transfer RNAs (tRNAs) play an essential role in mRNA translation by delivering amino acids to growing polypeptide chains. Recent data demonstrate that tRNAs can be cleaved by ribonucleases, and the resultant cleavage products, tRNA-derived small RNAs (tsRNAs), have crucial roles in physiological and pathological conditions. They are classified into more than six types according to their size and cleavage positions. Since the initial discovery of the physiological functions of tsRNAs more than a decade ago, accumulating data have demonstrated that tsRNAs play critical roles in gene regulation and tumorigenesis. These tRNA-derived molecules have various regulatory functions at the transcriptional, post-transcriptional, and translational levels. More than a hundred types of modifications are found on tRNAs, affecting the biogenesis, stability, function, and biochemical properties of tsRNA. Both oncogenic and tumor suppressor functions have been reported for tsRNAs, which play important roles in the development and progression of various cancers. Abnormal expression patterns and modification of tsRNAs are associated with various diseases, including cancer and neurological disorders. In this review, we will describe the biogenesis, versatile gene regulation mechanisms, and modification-mediated regulation mechanisms of tsRNA as well as the expression patterns and potential therapeutic roles of tsRNAs in various cancers. Small RNAs: potential roles in cancer treatment A type of small RNA has been shown to be associated with cancer and neurological disorders, and could be used in treatment. Small noncoding RNAs, just a few tens of nucleotides in length, have been referred to as the “dark matter of the genome”, playing unexpected roles in gene regulation. Hak Kyun Kim at Chung-Ang University in Seoul, South Korea, and co-workers reviewed research into tRNA-derived small RNAs (tsRNAs), which are produced when transfer RNA molecules are cleaved by enzymes. More than a hundred types of tsRNA modifications have been identified, some of which are involved in generating tumors while others suppress cancer progression. Abnormal tsRNA expression patterns are closely associated with certain diseases, and could be used as biomarkers in clinical trials. Other tsRNAs could be engineered to combat cancer directly as therapeutics.