ArticleScientific reports2017
AlkB homolog 3-mediated tRNA demethylation promotes protein synthesis in cancer cells.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 215 papers.
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215 citing papers in PubMed, 293 citations in OpenAlex.
- The role, regulatory mechanisms, and therapeutic implications of FTO in gastrointestinal cancer.Genes & diseases · 2026Review
- It takes two to tango: the intersection of deubiquitinases and mMolecular cancer · 2026Review
- An ALKBH3 Inhibitor HUHS199 Suppresses Proliferation of Glioblastoma Cells by Targeting 1-Methyladenosine on GADD45A mRNA.Chemical biology & drug design · 2026Article
- RNA modifications as determinants of cancer cell death: from epitranscriptomic mechanisms to therapeutic targeting.Functional & integrative genomics · 2026Review
- pH Tunes the DNA Repair Efficiency and Strand Preference of the AlkB Family Enzymes.Chemical research in toxicology · 2026Article
- Cell-type-specific m1A dynamics are associated with microglial phenotypic transition and neuronal metabolic adaptation during spinal cord injury.PLoS computational biology · 2026Article
- tRNA methylation: functional insights and epitranscriptomic regulation.Cell communication and signaling : CCS · 2026Review
- The crucial role of m6A methylation modification in nasopharyngeal carcinoma.Discover oncology · 2026Review
- Epigenetic transcriptional regulation of skeletal aging: The emerging role of mJournal of orthopaedic translation · 2026Review
- Long Noncoding RNA Isoform Specificity and Chemical Modification on tRNA-Derived Fragments Leading to Divergent Functions.The American journal of pathology · 2026Review
- tRNA modifications in cancer: from molecular mechanisms to clinical translation.Biomarker research · 2026Review
- RNA modification-mediated multidimensional crosstalk: a novel perspective on gene expression regulation.Genome biology · 2026Review
- Targeting RNA binding proteins with small-molecule inhibitors: Advances, challenges, and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- Identification of Novel Alternative Transcripts of the Human ALKBH Gene Family and Investigation of Their Unique Expression Signatures in Cancer Cells.Current issues in molecular biology · 2026Article
- m6A RNA modification and its emerging roles in diseases: recent advances and therapeutic implications.Journal of translational medicine · 2026Review
- WDR5-H3K4me3 Epigenetic Axis Promotes TRMT6-Dependent tRNA MAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Transcriptional and epigenetic reprogramming, lineage plasticity and therapy resistance in prostate cancer.Journal of the National Cancer Center · 2026Review
- YTHDC1-Mediated mJournal of agricultural and food chemistry · 2026Article
- RNA modification systems as therapeutic targets.Nature reviews. Drug discovery · 2026Review
- PPIB and its role in prostate cancer: associations with transcriptomic and splicing alterations.Frontiers in oncology · 2026Article
155 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mammalian AlkB homolog (ALKBH) family of proteins possess a 2-oxoglutarate- and Fe(II)-dependent oxygenase domain. A similar domain in the Escherichia coli AlkB protein catalyzes the oxidative demethylation of 1-methyladenine (1-meA) and 3-methylcytosine (3-meC) in both DNA and RNA. AlkB homolog 3 (ALKBH3) was also shown to demethylate 1-meA and 3-meC (induced in single-stranded DNA and RNA by a methylating agent) to reverse the methylation damage and retain the integrity of the DNA/RNA. We previously reported the high expression of ALKBH3 in clinical tumor specimens and its involvement in tumor progression. In this study, we found that ALKBH3 effectively demethylated 1-meA and 3-meC within endogenously methylated RNA. Moreover, using highly purified recombinant ALKBH3, we identified N6-methyladenine (N6-meA) in mammalian transfer RNA (tRNA) as a novel ALKBH3 substrate. An in vitro translation assay showed that ALKBH3-demethylated tRNA significantly enhanced protein translation efficiency. In addition, ALKBH3 knockdown in human cancer cells impaired cellular proliferation and suppressed the nascent protein synthesis that is usually accompanied by accumulation of the methylated RNAs. Thus, our data highlight a novel role for ALKBH3 in tumor progression via RNA demethylation and subsequent protein synthesis promotion.
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