Transfer RNA (Transfer Ribonucleic Acid, tRNA) is the most abundant short-chain non-coding RNA molecule in the organism. It carries and transports amino acids, participates in protein translation, and is an important bridge connecting mRNA and protein. Although tRNA is widely present in organisms, different body genomes have different preferences for specific codons, which leads to differences in tRNA profiles. Codon preference will affect translation efficiency and accuracy. Therefore, changes in the tRNA profile will have a significant impact on a variety of cellular physiological processes.
tRNA profile and cell fate
Studies have shown that changes in the tRNA profile can affect the fate of cells during development. A series of life activities such as cell proliferation, cell differentiation and cell apoptosis are accompanied by changes in tRNA levels. There are obvious differences in codon usage between genes related to cell maintenance and genes related to cell polymorphism. The changes in the tRNA profile induced by cell proliferation and cell differentiation correspond to genes related to cell maintenance and cell polymorphism, respectively. In addition, cell maintenance related gene mRNA specifically induces expression in proliferating cells and tumor cells, suggesting that there is a direct correlation between transcription and translation.
tRNAiMet can significantly affect the entire tRNA expression profile, and further lead to the enhancement of cell metabolism and proliferation. tRNA can also affect the formation of apoptotic bodies mediated by cytochrome C, and participate in the regulation of cell apoptosis. Through in vitro microinjection of tRNA, the researchers found that tRNA can inhibit the cytochrome C-mediated apoptosis pathway. All in all, the tRNA profile can regulate the physiological state of cells in many ways.
The relationship between tRNA profile and disease
The tRNA profile can not only affect a variety of cell physiological states, but also play an important role in the occurrence and development of various diseases. For example, the expression disorder of tRNA can induce tumorigenesis. Therefore, the study of tRNA expression profile is of great significance for revealing the pathological mechanism of human diseases.
1.Cancer
Gingold et al. found that there are significant differences in tRNA expression profiles between tumor cells and differentiated cells. The expression of tRNA that is highly expressed in differentiated cells or cells in a resting state is inhibited in proliferating cells. Conversely, tRNAs that are highly expressed in proliferating cells have lower expression levels in differentiated or resting cells. The researchers also found that cancer cells can adjust the tRNA profile, which is conducive to their own development. By comparing the tRNA expression levels in breast cancer and normal breast tissues, Pavon-Eternod found that the tRNA in breast cancer cell nuclei and mitochondria has changed significantly, suggesting that tRNA can be used as a molecular marker for breast cancer.
2.Viral infection
As we all know, viral protein synthesis is completely dependent on the host’s translation system, including the use of tRNA libraries. Therefore, it is generally believed that the virus selectively adapts to the tRNA pool of the host cell. Since the use of host codons determines the host’s tRNA library, viral protein synthesis only has high translation efficiency when codons that are highly similar to the host gene are used. However, in many cases, the codon usage of the viral gene does not match the host gene. Studies have shown that the codon usage of the early genes of HIV-1 is highly similar to that of the host genes, while the late genes of HIV are not the case. In the later stage of virus infection, the host tRNA library is more suitable for protein translation of HIV. Therefore, the virus can adjust the host tRNA library to adapt to its own protein synthesis needs.
How to study tRNA?
CD Genomics provides efficient and quantitative tRNA sequencing based on the next generation sequencing methods for tRNA gene prediction, curation and annotation. Scientists there have developed state-of-the-art tRNA-seq methodologies integrating modification removal and small RNA sequencing optimized for tRNA to ensure the most reliable and accurate tRNA-seq data for study tRNA. In order to fully support the tRNA research, CD Genomics also provides a wide range of NGS or mass spectrometry-based technologies for tRNA modification profiling.
