Abstract
Genetic and epigenetic changes deregulate RNA and protein expression in cancer cells. In this regard, tumors exhibit an abnormal proteome in comparison to the corresponding normal tissues. Translation control is a crucial step in the regulation of gene expression regulation under normal and pathological conditions that ultimately determines cellular fate. In this context, evidence shows that transfer and ribosomal RNA (tRNA and rRNA) modifications affect the efficacy and fidelity of translation. The number of RNA modifications increases with the complexity of organisms, suggesting an evolutionary diversification of the possibilities for fine-tuning the functions of coding and non-coding RNAs. In this review, we focus on alterations of modifications of transfer and ribosomal RNA that affect translation in human cancer. This variation in the RNA modification status can be the result of altered modifier expression (writers, readers or erasers), but also due to components of the machineries (C/D or H/ACA boxes) or alterations of proteins involved in modifier expression. Broadening our understanding of the mechanisms by which site-specific modifications modulate ribosome activity in the context of tumorigenesis will enable us to enrich our knowledge about how ribosomes can influence cell fate and form the basis of new therapeutic opportunities.
Highlights
Initial genetic studies in yeast and E. coli demonstrated that Ribosomal RNA (rRNA) modifications play an important role in ribosome function [2–4], supported by further research in the area in the early 2000s [5]
Ribosomal RNA The ribosome is a complex system that translates the nucleotide code of messenger RNA into protein in cells. This complex machinery comprises four ribosomal RNAs that are synthesized by polymerases I and III, and 80 ribosomal proteins (RPs) transcribed by polymerase II [46], all of which are organized in a large 60S subunit and a small 40S subunit
Ribosome heterogeneity is the result of various changes including those in the diversity of the composition of RPs and RPs mutations, abnormalities in rRNA modifications during ribosomal
Summary
Nucleotide modifications arise in most classes of RNA and more than 160 modifications are known [1]. In the context of human cancer, after a brief description of the type of RNA and the machineries involved, we summarize the modifications that have been functionally characterized (Fig. 1; Tables 1 and 2). Ribosomal RNA The ribosome is a complex system that translates the nucleotide code of messenger RNA into protein in cells. In humans, this complex machinery comprises four ribosomal RNAs (the 28S, 18S, 5.8S and 5S rRNAs) that are synthesized by polymerases I and III, and 80 ribosomal proteins (RPs) transcribed by polymerase II [46], all of which are organized in a large 60S subunit and a small 40S subunit. Ribosome heterogeneity is the result of various changes including those in the diversity of the composition of RPs and RPs mutations, abnormalities in rRNA modifications during ribosomal
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