Dynamic Regulation of tRNA Modifications in Cancer

Close, Pierre; Bose, Debojit; Chariot, Alain; Leidel, Sebastian A.

doi:10.1016/b978-0-12-811022-5.00010-3

Cited by 12 publications

(13 citation statements)

References 171 publications

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“…These kinds of biological modifications exercise important regulation functions during both normal and pathological bioprocesses and tissue development. Importantly, RNA modifications, especially N 6 -methyladenosine (m 6 A) modification, are shown to be essential for tumor development [22][23][24][25].In this review, we summarize the most recent advances in RNA modifications, especially the functions of m 6 A writers, erasers and readers, and their molecular mechanisms of action in GBM, so as to provide some clues for the development of new strategies for GBM treatment.…”

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confidence: 99%

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The Emerging Roles of RNA Modifications in Glioblastoma

Dong

Cui

2020

Cancers

103

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Glioblastoma (GBM) is a grade IV glioma that is the most malignant brain tumor type. Currently, there are no effective and sufficient therapeutic strategies for its treatment because its pathological mechanism is not fully characterized. With the fast development of the Next Generation Sequencing (NGS) technology, more than 170 kinds of covalent ribonucleic acid (RNA) modifications are found to be extensively present in almost all living organisms and all kinds of RNAs, including ribosomal RNAs (rRNAs), transfer RNAs (tRNAs) and messenger RNAs (mRNAs). RNA modifications are also emerging as important modulators in the regulation of biological processes and pathological progression, and study of the epi-transcriptome has been a new area for researchers to explore their connections with the initiation and progression of cancers. Recently, RNA modifications, especially m6A, and their RNA-modifying proteins (RMPs) such as methyltransferase like 3 (METTL3) and α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5), have also emerged as important epigenetic mechanisms for the aggressiveness and malignancy of GBM, especially the pluripotency of glioma stem-like cells (GSCs). Although the current study is just the tip of an iceberg, these new evidences will provide new insights for possible GBM treatments. In this review, we summarize the recent studies about RNA modifications, such as N6-methyladenosine (m6A), N6,2′O-dimethyladenosine (m6Am), 5-methylcytosine (m5C), N1-methyladenosine (m1A), inosine (I) and pseudouridine (ψ) as well as the corresponding RMPs including the writers, erasers and readers that participate in the tumorigenesis and development of GBM, so as to provide some clues for GBM treatment.

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confidence: 99%

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confidence: 99%

The Emerging Roles of RNA Modifications in Glioblastoma

Dong

Cui

2020

Cancers

103

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“…Reduced tRNA modifications, as a consequence of mutations or impaired function of tRNA-modifying enzymes or increased demethylase activity, may also lead to tRNA fragmentation [52][53][54][55][56]. Dysregulated tRNA fragmentation has been detected in different diseases [35,36] including cancer [45,54,57,58], neurological disorders [52,[59][60][61][62], metabolic disorders [30,31,53,55], and osteoarthritis [63].…”

Section: Trna Fragments a New Class Of Small Noncoding Rnasmentioning

confidence: 99%

tRNA Biology in the Pathogenesis of Diabetes: Role of Genetic and Environmental Factors

Arroyo

Green²,

Cnop³

et al. 2021

IJMS

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The global rise in type 2 diabetes results from a combination of genetic predisposition with environmental assaults that negatively affect insulin action in peripheral tissues and impair pancreatic β-cell function and survival. Nongenetic heritability of metabolic traits may be an important contributor to the diabetes epidemic. Transfer RNAs (tRNAs) are noncoding RNA molecules that play a crucial role in protein synthesis. tRNAs also have noncanonical functions through which they control a variety of biological processes. Genetic and environmental effects on tRNAs have emerged as novel contributors to the pathogenesis of diabetes. Indeed, altered tRNA aminoacylation, modification, and fragmentation are associated with β-cell failure, obesity, and insulin resistance. Moreover, diet-induced tRNA fragments have been linked with intergenerational inheritance of metabolic traits. Here, we provide a comprehensive review of how perturbations in tRNA biology play a role in the pathogenesis of monogenic and type 2 diabetes.

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“…In addition, many human tRNAs that have an A at the wobble base have a modification from A to I (inosine), which allows base pairing from A34-U to I34-U, I34-C or, in some cases, even to I34-A, increasing the encoding capacity of the modified tRNAs (Novoa et al, 2012;Pan, 2018). Enzymes that catalyse U34 modifications have been implicated in cancer and neurological diseases (Close et al, 2018). For example, the Elongator complex is required for a subset of tRNA modifications at U34 to promote efficient decoding of G-and A-ending codons.…”

Section: Trna Wobble Position and Decodingmentioning

confidence: 99%

Control of translation elongation in health and disease

Knight

Garland

Pöyry

et al. 2020

Disease Models &Amp; Mechanisms

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Regulation of protein synthesis makes a major contribution to posttranscriptional control pathways. During disease, or under stress, cells initiate processes to reprogramme protein synthesis and thus orchestrate the appropriate cellular response. Recent data show that the elongation stage of protein synthesis is a key regulatory node for translational control in health and disease. There is a complex set of factors that individually affect the overall rate of elongation and, for the most part, these influence either transfer RNA (tRNA)-and eukaryotic elongation factor 1A (eEF1A)-dependent codon decoding, and/or elongation factor 2 (eEF2)-dependent ribosome translocation along the mRNA. Decoding speeds depend on the relative abundance of each tRNA, the cognate:near-cognate tRNA ratios and the degree of tRNA modification, whereas eEF2-dependent ribosome translocation is negatively regulated by phosphorylation on threonine-56 by eEF2 kinase. Additional factors that contribute to the control of the elongation rate include epigenetic modification of the mRNA, coding sequence variation and the expression of eIF5A, which stimulates peptide bond formation between proline residues. Importantly, dysregulation of elongation control is central to disease mechanisms in both tumorigenesis and neurodegeneration, making the individual key steps in this process attractive therapeutic targets. Here, we discuss the relative contribution of individual components of the translational apparatus (e.g. tRNAs, elongation factors and their modifiers) to the overall control of translation elongation and how their dysregulation contributes towards disease processes.

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Dynamic Regulation of tRNA Modifications in Cancer

Cited by 12 publications

References 171 publications

The Emerging Roles of RNA Modifications in Glioblastoma

The Emerging Roles of RNA Modifications in Glioblastoma

tRNA Biology in the Pathogenesis of Diabetes: Role of Genetic and Environmental Factors

Control of translation elongation in health and disease

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