EC Number   |
General Information |
Reference |
|---|
   2.1.1.202 | malfunction |
exposure to oxidative stress efficiently repressed NSUN2, causing a reduction of methylation at specific tRNA sites. Loss of NSUN2 alters the biogenesis of tRNA-derived noncoding fragments (tRFs) in response to stress, leading to impaired regulation of protein synthesis. The intracellular accumulation of a specific subset of tRFs correlates with the dynamic repression of global protein synthesis. Disruption of the Nsun2 gene in mice causes global hypomethylation of tRNAs and a developmental growth retardation. The abnormal development of tissues including brain and skin is the result of impaired stem cell differentiation. The expression of NSUN2 is highly dynamic within tissues. For instance, NSUN2 is absent in quiescent stem cells in hair follicle bulges (BGs), steadily increases in progenitor cells in the hair germ, and is highest in the growing (anagen) hair bulb |
758103 |
| 2.1.1.202 | malfunction |
in trm4a defective mutants, the cytosine 5-methylation profile is the same as wild-type, showing that TRM4A is not required for methylation of any of the detected tRNAs. In contrast for trm4b-1 and trm4b-2 mutants, a total of 18 sites have no detectable methylation and 7 sites have reduced methylation when compared to wild-type, the sites are corresponding to structural positions C48, C49, and C50. trdmt1/trm4b double mutants are hypersensitive to the antibiotic hygromycin B |
735864 |
| 2.1.1.202 | malfunction |
loss-of-function mutations in the NSUN2 gene in both mouse and human cause growth retardation and neurodevelopmental deficits including microcephaly, as well as defects in cognition and motor function. Loss of NSUN2-mediated methylation of tRNA increases their endonucleolytic cleavage by angiogenin, and 5' tRNA fragments accumulate in Nsun2-/- brains. Neural differentiation of NES cells is impaired by both NSUN2 depletion and the presence of angiogenin. Since repression of NSUN2 also inhibits neural cell migration toward the chemoattractant fibroblast growth factor 2, the impaired differentiation capacity in the absence of NSUN2 may be driven by the inability to efficiently respond to growth factors. Upper-layer neurons are decreased in Nsun2 knockout brains, phenotype, detailed overview |
758477 |
| 2.1.1.202 | malfunction |
loss-of-function mutations in the NSUN2 gene in both mouse and human cause growth retardation and neurodevelopmental deficits including microcephaly, as well as defects in cognition and motor function. Loss of NSUN2-mediated methylation of tRNA increases their endonucleolytic cleavage by angiogenin, and 5' tRNA fragments accumulate in Nsun2-/- brains. Neural differentiation of NES cells is impaired by both NSUN2 depletion and the presence of angiogenin. Since repression of NSUN2 also inhibits neural cell migration toward the chemoattractant fibroblast growth factor 2, the impaired differentiation capacity in the absence of NSUN2 may be driven by the inability to efficiently respond to growth factors. Upper-layer neurons are decreased in Nsun2 knockout brains, phenotype, detailed overview. In the developing Nsun2-/- mouse cerebral cortex, intermediate progenitors accumulate and upper-layer neurons decrease. .Loss of NSUN2-mediated methylation of tRNA increases their endonucleolytic cleavage by angiogenin, and 5' tRNA fragments accumulate in Nsun2 -/- brains |
758477 |
| 2.1.1.202 | malfunction |
mutations in TRM4B display defects in root development and decreased m5C peaks. TRM4B affects the transcript levels of the genes involved in root development, which is positively correlated with their mRNA stability and m5C levels |
757702 |
| 2.1.1.202 | malfunction |
NSUN2 is associated with Myc-induced proliferation of cancer cells, mitotic spindle stability, infertility in male mice, and the balance of selfrenewal and differentiation in skin stem cells. In humans NSUN2 mutations cause an autosomal recessive syndrome characterized by intellectual disability and mental retardation |
736856 |
| 2.1.1.202 | malfunction |
the absence of Trm4a, but not Trm4b, causes a mild resistance of Schizosaccharomyces pombe to calcium chloride. Absence of Trm4a, but not Trm4b, causes a mild resistance of Schizosaccharomyces pombe to calcium chloride. In trm4aDELTA mutants, the C34 methylation level drops to background levels (8%), whereas C49 methylation remains at 82%. m5C34 is at 94% in trm4bDELTA mutant, and m5C49 drops to 9%, thus confirming that Trm4a is responsible for m5C34 and Trm4b for m5C49 on tRNAProCGG in vivo |
-, 757846 |
| 2.1.1.202 | malfunction |
the absence of Trm4a, but not Trm4b, causes a mild resistance of Schizosaccharomyces pombe to calcium chloride. In trm4aDELTA mutants, the C34 methylation level drops to background levels (8%), whereas C49 methylation remains at 82%. m5C34 is at 94% in trm4bDELTA mutant, and m5C49 drops to 9%, thus confirming that Trm4a is responsible for m5C34 and Trm4b for m5C49 on tRNAProCGG in vivo |
-, 757846 |
| 2.1.1.202 | malfunction |
tRNAs lacking m5C48/49/50 modifications are bound more tightly by angiogenin, leading to accumulation of 5' tRNA-derived small RNA fragments, which trigger cellular stress and are implicated in disease. Expression of catalytically inactive forms of NSUN2, but not NSUN1, NSUN5, or NSUN6, is reported to alter the total amount of m5C detected in the mRNA pool. svRNA4 acts analogously to a microRNA and a concomitant increase in the levels of the svRNA4 target mRNAs CACNG7 and CACNG8 is observed in NSUN2-/- cells. Loss of function mutations in NSUN2 underlie several neurodevelopmental disorders. A homozygous mutation in the NSUN2 gene that leads to the substitution of Gly679 for Arg (p.Gly679Arg) in the protein has been detected in individuals with autosomal-recessive intellectual disability. This amino acid substitution is suggested to impede NSUN2 function by preventing localization of the protein to its site of action in the nucleolus. NSUN2 has also been linked to Dubowitz syndrome, which is characterized by microcephaly, growth and mental retardation, eczema, and characteristic facial features. A homozygous mutation in the canonical splice acceptor of exon 6 leads to use of a cryptic splice donor, instability of the NSUN2 mRNA, a significant decrease in protein levels, and reduced methylation of NSUN2 target RNAs (m5C47/48 of tRNAAsp(GUC) |
756866 |
| 2.1.1.202 | malfunction |
yeast strains depleted of tRNAHis guanylyltransferase accumulate uncharged tRNAHis lacking the G-1 residue and subsequently accumulate additional 5-methylcytidine (m5C) at residues C48 and C50 of tRNAHis, due to the activity of the m5Cmethyltransferase Trm4. The increase in tRNAHis m5C levels does not require loss of Thg1, loss of G-1 of tRNAHis, or cell death but is associated with growth arrest following different stress conditions. Substantially increased tRNAHis m5C levels occur after temperature-sensitive strains are grown at nonpermissive temperature, and after wild-type strains are grown to stationary phase, starved for required amino acids, or treated with rapamycin. More modest accumulations of m5C in tRNAHis occur after starvation for glucose and after starvation for uracil. In virtually all cases examined, the additional m5C on tRNAHis occurs while cells are fully viable, and the increase is neither due to the GCN4 pathway, nor to increased Trm4 levels, phenotypes, overview. The increased amount of m5C is specific to tRNAHis. tRNAVal(AAC), which also normally has unmodified C48 and C50 residues adjacent to m5C49, has only marginally increased levels of m5C 7 h after temperature shift in the fcp1-1ts mutant |
-, 737227 |
