anticodon and Neoplasms

Transfer RNAs (tRNAs) play pivotal roles in the transmission of genetic information, and abnormality of tRNAs directly leads to translation disorders and causes diseases, including cancer. The complex modifications enable tRNA to execute its delicate biological function. Alteration of appropriate modifications may affect the stability of tRNA, impair its ability to carry amino acids, and disrupt the pairing between anticodons and codons. Studies confirmed that dysregulation of tRNA modifications plays an important role in carcinogenesis. Furthermore, when the stability of tRNA is impaired, tRNAs are cleaved into small tRNA fragments (tRFs) by specific RNases. Though tRFs have been found to play vital regulatory roles in tumorigenesis, its formation process is far from clear. Understanding improper tRNA modifications and abnormal formation of tRFs in cancer is conducive to uncovering the role of metabolic process of tRNA under pathological conditions, which may open up new avenues for cancer prevention and treatment.

Topics: Amino Acids; Anticodon; Humans; Neoplasms; RNA, Transfer

Transfer RNA (tRNA) plays a central role in translation by functioning as a biological link between messenger RNA (mRNA) and proteins. One prominent feature of the tRNA molecule is its heavily modified status, which greatly affects its biogenesis and function. Modifications within the anticodon loop are crucial for translation efficiency and accuracy, whereas other modifications in the body region affect tRNA structure and stability. Recent research has revealed that these diverse modifications are critical regulators of gene expression. They are involved in many important physiological and pathological processes, including cancers. In this review we focus on six different tRNA modifications to delineate their functions and mechanisms in tumorigenesis and tumor progression, providing insights into their clinical potential as biomarkers and therapeutic targets.

Topics: Anticodon; Humans; Neoplasms; RNA Processing, Post-Transcriptional; RNA, Transfer

Non-coding RNAs (ncRNAs) have been the focus of many studies over the last few decades, and their fundamental roles in human diseases have been well established. Transfer RNAs (tRNAs) are housekeeping ncRNAs that deliver amino acids to ribosomes during protein biosynthesis. tRNA fragments (tRFs) are a novel class of small ncRNAs produced through enzymatic cleavage of tRNAs and have been shown to play key regulatory roles similar to microRNAs. Development and application of high-throughput sequencing technologies has provided accumulating evidence of dysregulated tRFs in cancer. Aberrant expression of tRFs has been found to participate in cell proliferation, invasive metastasis, and progression in several human malignancies. These newly identified functional tRFs also have great potential as new biomarkers and therapeutic targets for cancer treatment. In this review, we focus on the major biological functions of tRFs including RNA silencing, translation regulation, and epigenetic regulation; summarize recent research on the roles of tRFs in different types of cancer; and discuss the potential of using tRFs as clinical biomarkers for cancer diagnosis and prognosis and as therapeutic targets for cancer treatment.

Topics: Anticodon; Biomarkers, Tumor; Early Detection of Cancer; Epigenesis, Genetic; Forecasting; Gene Silencing; High-Throughput Nucleotide Sequencing; Humans; Neoplasms; Oligonucleotides, Antisense; Prognosis; Protein Biosynthesis; RNA Precursors; RNA, Neoplasm; RNA, Transfer; RNA, Untranslated

Ribonucleotide modifications perform a wide variety of roles in synthesis, turnover and functionality of tRNA molecules. The presence of particular chemical moieties can refine the internal interaction network within a tRNA molecule, influence its thermodynamic stability, contribute novel chemical properties and affect its decoding behavior during mRNA translation. As the lack of specific modifications in the anticodon stem and loop causes disrupted proteome homeostasis, diminished response to stress conditions, and the onset of human diseases, the underlying modification cascades have recently gained particular scientific and clinical interest. Nowadays, a complicated but conclusive image of the interconnectivity between different enzymatic modification cascades and their resulting tRNA modifications emerges. Here we summarize the current knowledge in the field, focusing on the known instances of cross talk among the enzymatic tRNA modification pathways and the consequences on the dynamic regulation of the tRNA modificome by various factors. This article is part of a Special Issue entitled: SI: Regulation of tRNA synthesis and modification in physiological conditions and disease edited by Dr. Boguta Magdalena.

Topics: Animals; Anticodon; Endoribonucleases; Eukaryotic Cells; Humans; Mitochondrial Diseases; Models, Molecular; Multiprotein Complexes; Neoplasms; Nervous System Diseases; Nucleic Acid Conformation; Protein Biosynthesis; RNA Processing, Post-Transcriptional; RNA Stability; RNA-Binding Proteins; RNA, Fungal; RNA, Neoplasm; RNA, Transfer; Saccharomyces cerevisiae Proteins; Schizosaccharomyces pombe Proteins; tRNA Methyltransferases; Uridine

A dichotomous choice for metazoan cells is between proliferation and differentiation. Measuring tRNA pools in various cell types, we found two distinct subsets, one that is induced in proliferating cells, and repressed otherwise, and another with the opposite signature. Correspondingly, we found that genes serving cell-autonomous functions and genes involved in multicellularity obey distinct codon usage. Proliferation-induced and differentiation-induced tRNAs often carry anticodons that correspond to the codons enriched among the cell-autonomous and the multicellularity genes, respectively. Because mRNAs of cell-autonomous genes are induced in proliferation and cancer in particular, the concomitant induction of their codon-enriched tRNAs suggests coordination between transcription and translation. Histone modifications indeed change similarly in the vicinity of cell-autonomous genes and their corresponding tRNAs, and in multicellularity genes and their tRNAs, suggesting the existence of transcriptional programs coordinating tRNA supply and demand. Hence, we describe the existence of two distinct translation programs that operate during proliferation and differentiation.

Topics: Anticodon; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic; Codon; Histones; Humans; Neoplasms; Protein Biosynthesis; RNA, Messenger; RNA, Transfer; Transcriptome

In this article a new class of anticancer and antiviral drugs is discussed. These new drugs consist of small di- and tri-peptides, designed to bind to single-stranded (ss) regions that are crucial for the expression of genes such as the c-myc oncogene in cancers and start sites (and other ss regions) of viral pathogenic genes. The components (i.e. the amino acids and the sequences they form) of these peptides could be dictated by the specific binding of amino acids to their ss anticodons in tRNA. Cancer cell viability depends on the continued overexpression of the c-myc oncogene, and thus this gene is a target of opportunity for anticancer agents. Sharply reducing the overexpression of c-myc leads to the death of cancer cells. To achieve this end the following rationale is suggested: crucial regions of the c-myc promoters (to which activating proteins must bind for expression to occur) are single stranded and thus strongly resemble the anticodon loop of tRNA. It was found that amino acids chemically bind to their cognate tRNA anticodons. Regarding the ss regions of c-myc as a series of adjacent 'anticodons', di- and tri-peptides are proposed to be aligned to their cognate 'anticodons' in the proper order. For example, if the ss region of a promoter is hypothetically TTT-GGG-CCC, the tripeptide Lys-Pro-Gly could be expected to bind to it and deny access of the promoter to all activating proteins, thereby blocking c-myc expression and all the cancers dependent on such overexpression. Similarly, it is reported that in the initial phase of gene expression the start sites of the genes are single stranded (before and after and spanning the start site). Thus, invoking the amino acid cognate anticodon binding specificity (ACABS) principle as described above, a series of small peptides are suggested that could span the start sites of pathogenic viral genes (e.g. the oris region of herpes simplex virus (HSV)) to deny access of the gene to the transcription elements. This would inactivate the toxic effect of the virus and thereby constitute a promising approach to antiviral therapy, where the start sites (or other ss regions of pathogenic genes) have been sequenced. The ACABS principle (for peptide-nucleic-acid interaction) enables us to focus on probable effective small peptides rather than having to screen a large number of randomly chosen small peptides to find probable anticancer and antiviral therapeutic agents.

Topics: Animals; Anticodon; Antineoplastic Agents; Antiviral Agents; Binding Sites; Humans; Neoplasms; Oligopeptides; Oncogenes; Promoter Regions, Genetic; RNA, Transfer; Substrate Specificity

Constant generation of Reactive oxygen species (ROS) during normal cellular metabolism of an organism is generally balanced by similar rate of consumption by antioxidants. Imbalance between ROS production and antioxidant defense results in increased level of ROS causing oxidative stress which leads to promotion of malignancy. Queuine is a hyper modified base analogue of guanine, found at first anti-codon position of Q- family of tRNAs. These tRNAs are completely modified with respect to queuosine in terminally differentiated somatic cells, however hypomodification of Q-tRNAs is close association with cell proliferation. Q-tRNA modification is essential for normal development, differentiation and cellular functions. Queuine is a nutrient factor to eukaryotes. It is found to promote cellular antioxidant defense system and inhibit tumorigenesis. The activities of antioxidant enzymes like catalase, SOD, glutathione peroxidase and glutathione reductase are found to be low in Dalton's lymphoma ascites transplanted (DLAT) mouse liver compared to normal. However, exogenous administration of queuine to DLAT mouse improves the activities of antioxidant enzymes. The results suggest that queuine promotes antioxidant defense system by increasing antioxidant enzyme activities and in turn inhibits oxidative stress and tumorigenesis.

Topics: Animals; Anticodon; Antioxidants; Gene Expression Regulation; Guanine; Liver; Lymphocytes; Male; Mice; Neoplasm Transplantation; Neoplasms; Oxidative Stress; Reactive Oxygen Species; Time Factors