tRNA related research background

A. Overview
Transfer Ribonucleic Acid (tRNA) is the most abundant short-chain non-coding RNA molecule in the organism. It carries and transports amino acids and participates in protein translation. It is an important bridge connecting mRNA and protein. Although tRNA is widely present in living organisms, different organism genomes have different preferences for specific codons, resulting in differences in tRNA profiles. Codon preference affects translation efficiency and accuracy [1-3]. Therefore, changes in the tRNA profile can have a significant impact on a variety of cellular physiological processes. Arraystar's nrStarTM Human tRNA Repertoire PCR Array contains 66 pairs of nuclear tRNA primers and 22 pairs of mitochondrial tRNA primers, allowing researchers to easily and quickly analyze tRNA profiles. This product contains all the anti-codons provided by GtRNAdb and tRNAdb and is a powerful tool for studying human tRNA profiles.

B. tRNA profile and cell fate
Studies have shown that changes in the tRNA profile can influence fate decisions during cell development. A series of life activities such as cell proliferation [4], cell differentiation [4, 5] and apoptosis [6] are accompanied by changes in tRNA levels. There are significant differences in codon usage between genes involved in cell maintenance-related genes and cell polymorphisms. The tRNA profile changes induced by cell proliferation and cell differentiation correspond to cell maintenance-related genes and cell polymorphism genes, respectively (Fig. 1). In addition, cell maintenance-related gene mRNA specifically induces expression in proliferating cells and tumor cells, suggesting a direct correlation between transcription and translation [4]. Overexpression of the initiating tRNA (tRNAiMet) can significantly affect the entire tRNA expression profile and further lead to an increase in cellular metabolic capacity and proliferative capacity [5]. tRNA can also affect cytochrome C-mediated apoptotic body formation and participate in the regulation of apoptosis [6]. By microinjection of tRNA in vitro, the researchers found that tRNA can inhibit the cytochrome C-mediated apoptotic pathway [7]. In summary, the tRNA profile can regulate the physiological state of a cell in a variety of ways.

Figure 1. The tRNA profile is adapted to changes in the transcriptome.

C. tRNA spectrum and disease
The tRNA spectrum not only affects the physiological state of a variety of cells, but also plays an important role in the development of various diseases. For example, the expression disorder of tRNA can induce tumorigenesis [5]. Therefore, tRNA expression profiling research is of great significance for revealing the pathological mechanism of human diseases.

Cancer Gingold et al. found that tRNA expression profiles are significantly different between tumor cells and differentiated cells [4]. The expression of tRNA 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 a lower expression level in differentiated or resting cells. The researchers also found that cancer cells can adjust the tRNA spectrum to facilitate their own development. By comparing the expression levels of tRNA in breast cancer and normal breast tissue, Pavon-Eternod found significant changes in tRNA in the nucleus and mitochondria of breast cancer cells, suggesting that tRNA can be used as a molecular marker for breast cancer [12]. Recently, Goodarzi et al. also demonstrated that certain specific tRNA expression levels are elevated in breast cancer cells during their ability to metastasize. They believe that changes in tRNAGlu-UUC and tRNAArg-CCG expression levels may be one of the predisposing factors for breast cancer metastasis. Further studies indicate that tRNAGlu-UUC can promote the expression of EXOSC2 and GRIPAP1 proteins, thereby promoting tumor metastasis [8]. In conclusion, the disorder of expression of tRNA has a profound effect on the occurrence and development of tumors [5, 8-15].

Huntington's disease Huntington's disease is a highly prevalent hereditary neurodegenerative disease caused by an increase in the end of the huntingtin protein polyglutamine. Analysis of the brain tissue of Huntington's disease patients revealed the presence of polyalanine and polyserine traces in polyglutamine. These polyamino acids may be due to a frameshift of the glutamine-encoding CAG reading frame, resulting in a GCA reading frame encoding alanine or an AGC reading frame encoding serine. Girstmair et al. found that insufficient expression of tRNAGln-CUG is the key to inducing transcoding errors. In addition, the ratio of glutamine to alanine affects the morphology of the frameshift translation protein. These results indicate that the expression disorder of tRNA and its resulting frameshift translation may be related to the occurrence of Huntington's disease and the heterogeneity of disease individuals [16].

Viral infections are well known and viral protein synthesis is completely dependent on the host's translation system, including the use of tRNA libraries. It is therefore generally accepted 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 has high translational efficiency only when using codons that are highly similar to the host gene. However, in many cases, the codon usage of the viral gene does not match the host gene. Pavon-Eternod found that influenza A (influenza A) and vaccinia virus can modulate the tRNA pool of infected hosts to adapt to the translation of their own genes [17]. Studies have also shown that the early genes of HIV (HIV-1) are highly similar to the codon usage of host genes, while the late genes of HIV are not. In the late stage of viral infection, the host tRNA library is more suitable for protein translation of HIV [18]. Therefore, the virus can adapt the host tRNA library to adapt to the needs of its own protein synthesis.

references
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