N4-acetylcytidine and other RNA modifications in epitranscriptome: insight into DNA repair and cancer development

Epigenomics, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 12

Published: March 5, 2025

N4-acetylcytidine (ac4C) is a post-transcriptional RNA modification that plays crucial role in the epitranscriptome, influencing gene expression and cellular function. This occurs at cytosine base, where an acetyl group installed to nitrogen 4th position (N4). co-transcription affects stability, structure, translation efficiency. Recent studies have uncovered potential link between modifications DNA repair mechanisms, suggesting ac4C-modified or methylated RNAs may interact with factors involved pathways; thus, response damage. Dysregulation of modified RNAs, including ac4C RNA, has been implicated cancer development, aberrant levels these contribute oncogenic transformation by altering genome stability key genes regulating cell proliferation, cycle progression, apoptosis. Understanding dynamics offers promising insights into epitranscriptome processes treatment.

Language: Английский

---

Toward the use of nanopore RNA sequencing technologies in the clinic: challenges and opportunities

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(5)

Published: Feb. 27, 2025

Abstract RNA molecules have garnered increased attention as potential clinical biomarkers in recent years. While short-read sequencing and quantitative polymerase chain reaction been the primary methods for quantifying abundance, they typically fail to capture critical post-transcriptional regulatory elements, such modifications, which are often dysregulated disease contexts. A promising cutting-edge technique method that addresses this gap is direct sequencing, offered by Oxford Nanopore Technologies, can simultaneously both abundance modification information. The rapid advancements platform, along with growing evidence of species biofluids, presents a compelling opportunity. In review, we discuss challenges emerging opportunities adoption nanopore technologies clinic, highlighting their revolutionize personalized medicine monitoring.

Language: Английский

---

Queuosine tRNA Modification: Connecting the Microbiome to the Translatome

BioEssays, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

ABSTRACT Transfer RNA (tRNA) modifications play an important role in regulating mRNA translation at the codon level. tRNA can influence selection and optimality, thus shifting toward specific sets of mRNAs a dynamic manner. Queuosine (Q) is modification occurring wobble position. In eukaryotes, queuosine synthesized by tRNA‐guanine trans ‐glycosylase (TGT) complex, which incorporates nucleobase queuine (or Qbase) into guanine GUN anticodons. Queuine sourced from gut bacteria dietary intake. Q was recently shown to be critical for cellular responses oxidative mitochondrial stresses, as well its potential neurodegenerative diseases brain health. These unique features provide interesting insight regulation bacteria, health implications. this review, biology examined light recent literature nearly 4 decades research. Q's neuropsychiatric cancer highlighted discussed. Given interest Q, new findings, more research needed fully comprehend biological function disease relevance, especially neurobiology.

Language: Английский

---

Closing in on human methylation—the versatile family of seven-β-strand (METTL) methyltransferases

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Abstract Methylation is a common biochemical reaction, and number of methyltransferase (MTase) enzymes mediate the various methylation events occurring in living cells. Almost all MTases use methyl donor S-adenosylmethionine (AdoMet), and, humans, largest group AdoMet-dependent are so-called seven-β-strand (7BS) MTases. Collectively, 7BS target wide range biomolecules, i.e. nucleic acids proteins, as well several small metabolites signaling molecules. They play essential roles key processes such gene regulation, protein synthesis metabolism, neurotransmitter clearance. A decade ago, roughly half human had been characterized experimentally, whereas remaining ones merely represented hypothetical predicted from bioinformatics analysis, many which were denoted METTLs (METhylTransferase-Like). Since then, considerable progress has made, function > 80% uncovered. In this review, I provide an overview (estimated) 120 MTases, grouping them according to substrate specificities sequence similarity. also elaborate on challenges faced when studying these describe recent major advances field.

Language: Английский

---

Hydroxy‐wybutosine tRNA modifications as indicators of disease progression and therapeutic targets in leukaemia

British Journal of Haematology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 10, 2024

Therapeutic approaches for acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) differ due to distinct diagnostic criteria treatment strengths. However, reliable biomarkers differentiate AML from MDS are needed. This study investigated transfer RNA (tRNA) modifications, particularly hydroxy-wybutosine (OHyW), in the transition AML. We found a significant decrease OHyW its biosynthetic enzyme leucine carboxyl methyltransferase 2 (LCMT2, alias symbol is TYW4) levels compared MDS. Mass spectrometric analysis revealed tRNA modification patterns, with showing decreased increased precursor levels, indicating disrupted pathway. Lower LCMT2 expression correlated reduced drug sensitivity limited differentiation potential cell lines. The results highlight pivotal role of modifications progression suggest that targeting may enhance therapeutic outcomes By understanding these molecular mechanisms, we can develop new markers strategies, potentially transforming clinical management improving patient outcomes.

Language: Английский

---

Chemotherapeutic agents and leucine deprivation induce codon-biased aberrant protein production in cancer

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

Abstract Messenger RNA (mRNA) translation is a tightly controlled process frequently deregulated in cancer. Key to this deregulation are transfer RNAs (tRNAs), whose expression, processing and post-transcriptional modifications often altered cancer support cellular transformation. In conditions of limiting levels amino acids, control protein synthesis leads aberrant production the form ribosomal frameshifting or misincorporation non-cognate acids. Here, we studied leucine, an essential acid coded by six different codons. Surprisingly, found that leucine deprivation stalling various cell types, predominantly at one codon, UUA. Similar effects were observed after treatment with chemotherapeutic agents, implying shared mechanism controlling downstream on mRNA translation. both conditions, limitation availability tRNALeu(UAA) for was shown be cause dominant effect UUA The induced proteins can processed immune-presented as neoepitopes direct T-cell killing. Altogether, uncovered novel mode interplay between DNA damage, regulation tRNA could exploited anti-cancer therapy.

Language: Английский

---

Editorial: Translational control in cancer

NAR Cancer, Journal Year: 2024, Volume and Issue: 6(3)

Published: July 9, 2024

---

Variation of tRNA modifications with and without intron dependency

Frontiers in Genetics, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 4, 2024

tRNAs have recently gained attention for their novel regulatory roles in translation and diverse functions beyond translation. One of the most remarkable aspects tRNA biogenesis is incorporation various chemical modifications, ranging from simple base or ribose methylation to more complex hypermodifications such as formation queuosine wybutosine. Some are transcribed intron-containing pre-tRNAs. While majority these modifications occur independently introns, some catalyzed an intron-inhibitory manner, certain cases, they intron-dependent manner. This review focuses on pre-tRNA modification, including pre-tRNA, both fashions. Any perturbations modification processing may lead a range diseases disorders, highlighting importance understanding mechanisms molecular biology medicine.

Language: Английский

---

ADAT2/3-mediated tRNA editing promotes cancer cell growth and tumorigenicity

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 3, 2024

Abstract Transfer RNAs (tRNAs) are subject to various chemical modifications that influence their stability or function. Adenosine Inosine (A-to-I) editing in the tRNA anticodon at position A34 is an important modification expands anticodon-codon recognition wobble and required for normal mRNA translation. The relevance of cancer remains unexplored. Here we show genes encoding ADAT2/3 deaminase complex, responsible A-to-I humans, commonly amplified and/or overexpressed several tumor types including liposarcoma (LPS). We find knockdown ADAT complex suppresses LPS cell growth tumorigenicity. Mechanistically, decreased upon ADAT2 depletion leads defective translation a subset mRNAs. Thus, ADAT-mediated promotes oncogenesis by enhancing promoting mRNAs enriched NNC codons lack cognate tRNAs therefore depend on A-I decoding Our results uncover oncogenic role identify as potential new therapeutic target.

Language: Английский

---