EC Number   |
General Information |
Reference |
|---|
   2.1.1.203 | evolution |
nonessential tRNA modifications by methyltransferases are evolutionarily conserved and have been reported to stabilize mature tRNA molecules and prevent rapid tRNA decay. The tRNA modifying enzymes, NSUN2 and METTL1, EC 2.1.1.33, are mammalian orthologues of yeast Trm4 and Trm8, which are required for protecting tRNA against tRNA decay |
737060 |
| 2.1.1.203 | malfunction |
combined knockdown of NSUN2 and METTL1, EC 2.1.1.33, in HeLa cells drastically potentiate sensitivity of cells to 5-fluorouracil, but does not affect cisplatin- and paclitaxel-induced cytotoxicity, synergistic effects of NSUN2 and METTL1 double knockdown, which causes rapid tRNA(ValAAC) degradation induced by destabilizing 5-fluorouracil |
737060 |
| 2.1.1.203 | malfunction |
in mice, a Nsun2 knockout, ablation of Nsun2 through the deletion of exon 8, leads to the gross small-size phenotype indicating weight loss with 30% reduction at 3 months old, and partial alopecia at about 10 months old, suggesting a role for NSUN2 in skin homeostasis. Nsun2-/- males are sterile. Heterozygous mice appear normal and have no visible phenotype |
718539 |
| 2.1.1.203 | malfunction |
in the absence of NSun2, tRNAs lack specific cytosine-5 methylation modifications, which can cause reduced protein translation rates. In NSun2-depleted testes, genes encoding Ddx4, Miwi, and Tudor domain-containing (Tdr) proteins are repressed, indicating that RNA-processing and posttranscriptional pathways are impaired. Proteins of the RNA-processing machinery are reduced in NSun2-/- testes. Loss of NSun2 specifically blocks meiotic progression of germ cells into the pachytene stage, as spermatogonial and Sertoli cells are unaffected in knockout mice. Lack of NSun2 causes a block of progression of the first prophase of male meiosis at the zygotene-pachytene stage before the chromatoid bodies first appear in the cytoplasm at the late pachytene stage. Phenotype, detailed overview |
734682 |
| 2.1.1.203 | malfunction |
loss-of-function mutations in the human NSUN3 gene causes mitochondrial disorders. NSUN2-depleted cells show attenuated changes to protein synthesis rates. Protein synthesis rates of rescued NSUN2-/- cells (NSUN2) are comparable to NSUN2+/+ cells and slightly, but not significantly, reduced when the enzymatic dead version of NSUN2 K190M is expressed. Cell stress causes a strong but temporary reduction of protein synthesis, which is attenuated by loss of NSUN2. Stress induces a site-specific and dynamic loss of m5C. Mitochondrial activity is reduced and catabolic pathways enhanced in the absence of NSUN2 |
758103 |
| 2.1.1.203 | malfunction |
mutation G679R causes NSUN2 to fail to localize within the nucleolus. NSUN2, besides other RNA-methyltransferase-encoding genes, is involved in neurological disorders like intellectual disability, also called mental retardation, phenotypes, overview |
718539 |
| 2.1.1.203 | malfunction |
mutation in (cytosine-5) RNA methyltransferase NSun2, which targets mostly tRNAs, impacts the expression of mobile element-derived sequences and affects DNA repeat integrity in Drosophila melanogaster. Reduced tRNA stability in the RCMT mutant indicates that tRNA-dependent processes affect mobile element expression and DNA repeat stability. NSun2 function affects mobile element expression and genome integrity in a heat shock-independent fashion. Reduced tRNA stability in both RCMT mutants indicates that tRNA-dependent processes affect mobile element expression and DNA repeat stability. NSun2 mutants show heat-shock-independent transposable element (TE) expression changes |
756399 |
| 2.1.1.203 | malfunction |
mutation of the cysteine in motif IV in human NSUN3 to alanine or serine results in a stable covalent intermediate |
756866 |
| 2.1.1.203 | malfunction |
mutation of the cysteine in motif IV in human NSUN3 to alanine or serine results in a stable covalent intermediate. Lack of NSUN3 (or ALKBH1) impairs mitochondrial translation, leading to decreased cell proliferation. Mutations in NSUN3 that lead to either aberrant splicing and frameshifting (p.Glu42Valfs*11) or the introduction of a premature stop codon (c.295C>T/p.Arg99*) have been detected in patients with a mitochondrial deficiency disorder characterized by developmental disability microcephaly, failure to thrive, recurrent increased lactate levels in plasma, muscular weakness, proximal accentuated, external ophthalmoplegia, and convergence nystagmus. Furthermore, mitochondrial disease-associated point mutations with the gene encoding mt-tRNAMet that lead to A37G and C39U substitutions have been shown to impede methylation of C34 by NSUN3. In both cases, lack of NSUN3-mediated modification impairs mitochondrial translation, leading to reduced mitochondrial function. Reduced mitochondrial translation affects the normal differentiation program |
756866 |
| 2.1.1.203 | malfunction |
NSUN3-knockout cells show strong reduction in mitochondrial protein synthesis and reduced oxygen consumption, leading to deficient mitochondrial activity. Reconstitution of formation of 5-methylcytidine (m5C) at position 34 (m5C34) on mt-tRNAMet with recombinant NSUN3 in the presence of AdoMet. Two disease-associated point mutations in mt-tRNAMet that impair m5C34 formation by NSUN3, are determined, indicating that a lack of f5C34 has pathological consequences. Loss of NSUN3 causes mitochondrial dysfunction, phenotype, overview |
757733 |
