tRNA Function and Dysregulation in Cancer

Abstract

Transfer RNA (tRNA) is a central component of protein synthesis and plays important roles in epigenetic regulation of gene expression in tumors. tRNAs are also involved in many cell processes including cell proliferation, cell signaling pathways and stress response, implicating a role in tumorigenesis and cancer progression. The complex role of tRNA in cell regulation implies that an understanding of tRNA function and dysregulation can be used to develop treatments for many cancers including breast cancer, colon cancer, and glioblastoma. Moreover, tRNA modifications including methylation are necessary for tRNA folding, stability, and function. In response to certain stress conditions, tRNAs can be cleaved in half to form tiRNAs, or even shorter tRNA fragments (tRF). tRNA structure and modifications, tiRNA induction of stress granule formation, and tRF regulation of gene expression through the repression of translation can all impact a cell's fate. This review focuses on how these functions of tRNAs, tiRNA, and tRFs can lead to tumor development and progression. Further studies focusing on the specific pathways of tRNA regulation could help identify tRNA biomarkers and therapeutic targets, which might prevent and treat cancers.

Keywords: TRF; cancer; protein; tRNA; tiRNA; tumor.

FIGURE 1

A schematic representation of the process of tRNA biogenesis. tRNA biogenesis begins with transcription of tRNA to form pre-tRNA. This pre-tRNA is then processed to form a mature tRNA before being exported from the nucleus. The mature tRNA is then ready to be charged with an amino acid by an aminoacyltRNA synthetase.

FIGURE 2

This diagram lists examples of tRNA hypermodification, tRNA hypomodification, tRNA gene expression, and tRNA-derived fragments that can lead to cancer development and spread. For tRNA hypermodification and tRNA hypomodification, the diagram includes tRNA modifications and tRNA methyltransferases associated with cancer development and spread.