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Literature summary for 2.1.1.203 extracted from

  • Bohnsack, K.; Hoebartner, C.; Bohnsack, M.
    Eukaryotic 5-methylcytosine (M5C) RNA methyltransferases mechanisms, cellular functions, and links to disease (2019), Genes (Basel), 10, 102 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.1.1.203

Protein Variants

Protein Variants Comment Organism
A37G naturally occurring mutation, mitochondrial disease-associated point mutations with the gene encoding mt-tRNAMet that lead to A37G substitution, impede methylation of C34 by NSUN3, lack of NSUN3-mediated modification impairs mitochondrial translation, leading to reduced mitochondrial function Homo sapiens
C39U naturally occurring mutation, mitochondrial disease-associated point mutations with the gene encoding mt-tRNAMet that lead to C39U substitution, impede methylation of C34 by NSUN3, lack of NSUN3-mediated modification impairs mitochondrial translation, leading to reduced mitochondrial function Homo sapiens
additional information mutation of the cysteine in motif IV in human NSUN3 to alanine or serine results in a stable covalent intermediate Saccharomyces cerevisiae
additional information mutation of the cysteine in motif IV in human NSUN3 to alanine or serine results in a stable covalent intermediate. 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 Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
mitochondrion NSUN3 has been shown to localize to the mitochondrial matrix, its mitochondrial import has not been determined Homo sapiens 5739
-
mitochondrion NSUN3 has been shown to localize to the mitochondrial matrix, its mitochondrial import has not been determined Saccharomyces cerevisiae 5739
-
additional information two of the seven NSUN proteins (NSUN3 and NSUN4) are synthesized on cytoplasmic ribosomes but localize to mitochondria Homo sapiens
-
-
additional information two of the seven NSUN proteins (NSUN3 and NSUN4) are synthesized on cytoplasmic ribosomes but localize to mitochondria Saccharomyces cerevisiae
-
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
S-adenosyl-L-methionine + cytosine34 in mitochondrial tRNAMet precursor Homo sapiens
-
 S-adenosyl-L-homocysteine + 5-methylcytosine34 in mitochondrial tRNAMet precursor
-
 ?
S-adenosyl-L-methionine + cytosine34 in mitochondrial tRNAMet precursor Saccharomyces cerevisiae
-
 S-adenosyl-L-homocysteine + 5-methylcytosine34 in mitochondrial tRNAMet precursor
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9H649
-
-
Saccharomyces cerevisiae Q9H649
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information the presence of a stable anticodon stem is found to be essential for formation of m5C34 of mt-tRNAMet by NSUN3 Saccharomyces cerevisiae ?
-
-
S-adenosyl-L-methionine + cytosine34 in mitochondrial tRNAMet precursor
-
 Homo sapiens S-adenosyl-L-homocysteine + 5-methylcytosine34 in mitochondrial tRNAMet precursor
-
 ?
S-adenosyl-L-methionine + cytosine34 in mitochondrial tRNAMet precursor
-
 Saccharomyces cerevisiae S-adenosyl-L-homocysteine + 5-methylcytosine34 in mitochondrial tRNAMet precursor
-
 ?

Synonyms

Synonyms Comment Organism
5-methylcytosine RNA methyltransferase
-
 Homo sapiens
5-methylcytosine RNA methyltransferase
-
 Saccharomyces cerevisiae
M5C RNA methyltransferase
-
 Homo sapiens
M5C RNA methyltransferase
-
 Saccharomyces cerevisiae
NSUN3
-
 Homo sapiens
NSUN3
-
 Saccharomyces cerevisiae

Cofactor

Cofactor Comment Organism Structure
S-adenosyl-L-methionine
-
 Homo sapiens
S-adenosyl-L-methionine
-
 Saccharomyces cerevisiae

General Information

General Information Comment Organism
malfunction mutation of the cysteine in motif IV in human NSUN3 to alanine or serine results in a stable covalent intermediate Saccharomyces cerevisiae
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 Homo sapiens
metabolism during the maturation of the cytoplasmic tRNALeu(CAA), an m5C34 modification is also installed by the multisite-specific NSUN2 (cf. EC 2.1.1.202) Homo sapiens
metabolism during the maturation of the cytoplasmic tRNALeu(CAA), an m5C34 modification is also installed by the multisite-specific NSUN2 (cf. EC 2.1.1.202) Saccharomyces cerevisiae
additional information catalytic mechanism of the enzyme, comparison of NSUN family enzymes, overview. The NSUN family enzymes use the cysteine located in amino acid motif VI for the nucleophilic attack on carbon 6 of the target cytosine in RNA. In all seven human NSUN variants, the catalytic cysteine is preceded by threonine. Hydrogen bonding with the backbone carbonyl of proline and the aspartate side chain in motif IV orients the base in the active site and assists bond formation by transient protonation of the endocyclic N3 of cytidine. The activated nucleobase then accepts a methyl group from the properly positioned SAM cofactor, resulting in the formation of a carbon-carbon bond and generation of S-adenosylhomocysteine (SAH). To complete the reaction, the covalently bound methylated RNA has to be released from the protein. This elimination is assisted by the cysteine located in motif IV of NSUN proteins. This cysteine is located next to the conserved proline and acts as a base to deprotonate the tetrahedral carbon and initiate the elimination reaction that restores the unsaturated m5C heterocycle Homo sapiens
additional information catalytic mechanism of the enzyme, comparison of NSUN family enzymes, overview. The NSUN family enzymes use the cysteine located in amino acid motif VI for the nucleophilic attack on carbon 6 of the target cytosine in RNA. In all seven human NSUN variants, the catalytic cysteine is preceded by threonine. Hydrogen bonding with the backbone carbonyl of proline and the aspartate side chain in motif IV orients the base in the active site and assists bond formation by transient protonation of the endocyclic N3 of cytidine. The activated nucleobase then accepts a methyl group from the properly positioned SAM cofactor, resulting in the formation of a carbon-carbon bond and generation of S-adenosylhomocysteine (SAH). To complete the reaction, the covalently bound methylated RNA has to be released from the protein. This elimination is assisted by the cysteine located in motif IV of NSUN proteins. This cysteine is located next to the conserved proline and acts as a base to deprotonate the tetrahedral carbon and initiate the elimination reaction that restores the unsaturated m5C heterocycle Saccharomyces cerevisiae
physiological function NSUN3 is a mitochondrial tRNA m5C methyltransferase that specifically targets the wobble position (C34) of mt-tRNAMet. Mt-tRNAMet-C34 is almost fully modified in vivo, and, although bisulfite and reduced bisulfite sequencing analyses indicate the presence of some m5C at this position, the majority undergoes further oxidation by ALKBH1 to generate 5-formylcytosine (f5C), structures of modified nucleotides at position 34 and the modification pathway. 5-Formylcytosine (f5C) has a well-established role in expanding codon recognition by mt-tRNAMet during mitochondrial translation. Modification of mt-tRNAMet by NSUN3 occurs in the mitochondria Saccharomyces cerevisiae
physiological function NSUN3 is a mitochondrial tRNA m5C methyltransferase that specifically targets the wobble position (C34) of mt-tRNAMet. The wobble base modification(s) installed by NSUN3 and ALKBH1 likely serve to expand codon recognition by mt-tRNAMet, enabling it to fulfil these diverse functions. Mt-tRNAMet-C34 is almost fully modified in vivo, and, although bisulfite and reduced bisulfite sequencing analyses indicate the presence of some m5C at this position, the majority undergoes further oxidation by ALKBH1 to generate 5-formylcytosine (f5C), structures of modified nucleotides at position 34 and the modification pathway. 5-Formylcytosine (f5C) has a well-established role in expanding codon recognition by mt-tRNAMet during mitochondrial translation. Modification of mt-tRNAMet by NSUN3 occurs in the mitochondria Homo sapiens