What is the Role of tRNA Methylation Modification in the Cell Cycle?
Post-transcriptional modifications of RNA molecules include methylation, acetylation deamination, isomerization, glycosylation, thiolation and pseudouracil modification among other types. Methylation represents the predominant post-transcriptional modification found within transfer RNA (tRNA) molecules. tRNA methylation has maintained its evolutionary conservation while also exhibiting dynamic and reversible properties within cellular environments. The stability of tRNA molecular conformation together with genome translation efficiency depend on this modification.
Many diseases including neurological disorders and tumors result from defective tRNA methylation. The dynamic regulation of tRNA methylation is coordinated by three types of enzymes: The writer methyltransferase complex adds methyl groups while the eraser demethylase complex removes them and the reader RNA modification binding protein recognizes these modifications. This modification system plays a crucial role in cellular biological processes such as tumor metabolism and immune regulation while also shaping the tumor microenvironment through control of translation efficiency and mitochondrial function along with tRNA fragment generation.
Through its impact on translation efficiency and mitochondrial function tRNA methylation modification also promotes tumor cell proliferation by controlling cell cycle-related protein expression. Cell cycle progression within cells is a critical biological function whose stoppage and progression rely entirely on cell cycle-related protein expressions. Tumor cells divide at a much faster rate than normal cells because they show significant dysregulation in cell cycle-related proteins. The altered activation states of cell cycle processes represent fundamental characteristics of tumors which scientists believe contribute majorly to tumor formation and progression. The potential to hinder tumor growth or boost drug effectiveness lies in the regulatory mechanisms of the cell cycle.
The cell cycle process requires precise control through the synthesis and degradation of specific proteins including cell cycle checkpoint proteins together with DNA replication-related enzymes and cell division regulatory factors. Tumor cells exhibit abnormal cell cycle regulation that facilitates their rapid proliferation and substantial protein and energy requirements. Methylation modifications in tRNA impact tRNA expression levels while also controlling translation efficiency to fulfill tumor cells’ protein demands and affect mitochondrial function and energy supply. The modification of tRNA methylation is essential for controlling the cell cycle in tumor cells. The rapid advancement of high-throughput sequencing technology has enabled scientists to identify and report numerous tRNA methylation modifications and their modifying enzymes which control cell cycle regulation. Tumor prevention and treatment research anticipates tRNA methylation modifications and their associated enzymes to serve as new therapeutic targets.
tRNA Methylation Modification and Its Modifying Enzymes
tRNA functions as a crucial linker molecule during protein synthesis while it ensures precise genetic information transfer from parent cells to daughter cells. tRNA needs multiple post-transcriptional modifications to preserve its secondary "cloverleaf" structure while transforming into an adaptable "L-shaped" tertiary configuration through folding and splicing. TRNA can be categorized into cytoplasmic tRNA (ctRNA) and mitochondrial tRNA (mtRNA) based on their mature positions which results in distinct structural and functional differences between the two forms. The ctRNA molecule consists of approximately 73 to 93 nucleotides while maintaining a characteristic cloverleaf structure through its anticodon loop, DHU loop, TΨC loop, and variable loop which performs the primary role in cellular protein synthesis. mtRNA contains 57 nucleotides which enable it to carry out mitochondrial protein translation. Its abnormal modification affects mitochondrial function, thereby regulating energy metabolism.
tRNA methylation modification types mainly include m1A, N6-methyladenosine (m6A), N7-methylguanosine modification (m7G), N2-methylguanosine (m2G), N1-methylguanosine (m1G), N3-methylcytidine (m3C), N5-methylcytidine (m5C), 5-methyluridine (m5U), etc