The enzyme, found in higher eukaryotes including insects and vertebrates, and their viruses, methylates the ribose of the ribonucleotide at the second transcribed position of mRNAs and snRNAs. This methylation event is known as cap2. The human enzyme can also methylate mRNA molecules where the upstream ribonucleotide is not methylated (see EC 2.1.1.57, methyltransferase cap1), but with lower efficiency .
The enzyme, found in higher eukaryotes including insects and vertebrates, and their viruses, methylates the ribose of the ribonucleotide at the second transcribed position of mRNAs and snRNAs. This methylation event is known as cap2. The human enzyme can also methylate mRNA molecules where the upstream ribonucleotide is not methylated (see EC 2.1.1.57, methyltransferase cap1), but with lower efficiency [2].
the recombinant enzyme produces a RNase T2-resistant RNA fragment, cap012, from cap01-RNA, but shows no activity with a purified BAP protein. Only a subset of labeled RNA molecules that has GpppG incorporated during transcription is a substrate for hMTr2. hMTr2 recognizes TMG-capped snRNAs in vitro
the recombinant enzyme produces a RNase T2-resistant RNA fragment, cap012, from cap01-RNA, but shows no activity with a purified BAP protein. Only a subset of labeled RNA molecules that has GpppG incorporated during transcription is a substrate for hMTr2. hMTr2 recognizes TMG-capped snRNAs in vitro
a conventional 5'-terminal structure of eukaryotic mRNAs consists of a 7-methylguanosine (m7G) moiety linked to the first transcribed nucleotide by a 5' to 5' triphosphate bridge resulting in the structure m7GpppN, which is referred to as cap 0, and most often the first and second transcribed nucleotide carry 2'-O-methyl groups (cap 1 and cap 2 structures, respectively). The cap2 methyltransferase, EC 2.1.1.296 transfers the methyl group to the second nucleotide. In contrast, four nucleotides adjacent to the m7G cap are methylated at the SL RNA 5' end to generate a cap 4 structure: m7G-ppp-N6,N6,2'-O-trimethyladenosine-p-2'-O-methyladenosine-p-2'-O-methylcytosine-p-N3,2'-O-methyluridine. The cap 4 structure seems to be restricted to the family Trypanosomatidae
the enzyme builds the cap 4 structure, usage of an assay with digestion with ribonuclease T2, to monitor the presence of 2'-O-modifications at positions +1 to +4 of the SL sequence
a conventional 5'-terminal structure of eukaryotic mRNAs consists of a 7-methylguanosine (m7G) moiety linked to the first transcribed nucleotide by a 5' to 5' triphosphate bridge resulting in the structure m7GpppN, which is referred to as cap 0, and most often the first and second transcribed nucleotide carry 2'-O-methyl groups (cap 1 and cap 2 structures, respectively). The cap2 methyltransferase, EC 2.1.1.296 transfers the methyl group to the second nucleotide. In contrast, four nucleotides adjacent to the m7G cap are methylated at the SL RNA 5' end to generate a cap 4 structure: m7G-ppp-N6,N6,2'-O-trimethyladenosine-p-2'-O-methyladenosine-p-2'-O-methylcytosine-p-N3,2'-O-methyluridine. The cap 4 structure seems to be restricted to the family Trypanosomatidae
neither N7 methylation of the guanosine cap nor 2'-O-ribose methylation of the first transcribed nucleotide are required for hMTr2, but the presence of cap1 methylation increases hMTr2 activity
neither N7 methylation of the guanosine cap nor 2'-O-ribose methylation of the first transcribed nucleotide are required for hMTr2, but the presence of cap1 methylation increases hMTr2 activity
the 5' cap of human messenger RNA contains 2'-O-methylation of the first and often second transcribed nucleotide that is important for its processing, translation and stability. Enzyme responsible for the methylations are CMTr1 and CMTr2, respectively
MT57 homologs are only found in trypanosomatid protozoa that have a cap 4 structure and in poxviruses, of which vaccinia virus is a prototype, TbMT48 or TbMT57 are two protein components of the cap 4 biosynthetic machinery
the enzyme belongs to the Rossmann-fold MTase (RFM) family, hMTr1 and hMTr2 are paralogues forming a subfamily with higher eukaryotic and viral members, minimum evolution tree of homologues of known 2'-O-ribose mRNA cap MTases, overview
the enzyme shows significant sequence and structural similarities to vaccinia virus VP39, another cap-specific RNA 2'-O-methyltransferase. TbMT48 or TbMT57 are two protein components of the cap 4 biosynthetic machinery
downregulation by RNAi or genetic ablation of TbMT57 result in the accumulation of SL RNA missing 2'-O-methyl groups at positions +3 and +4 and thus bearing a cap 2 rather than a cap 4. Genetic ablation of MT57 results in viable cells with no apparent defect in SL RNA transsplicing, suggesting that MT57 is not essential or that trypanosomes have developed alternate mechanisms to counteract the absence of this protein
TbMT48 or TbMT57 are two protein components of the cap 4 biosynthetic machinery. The enzymes involved in cap 4 biogenesis, TbMT48 and TbMT57, are encoded by non-essential genes, considering that the SL cap 4 structure is a crucial determinant for trans-splicing competence of the SL RNA
the 5' cap of human messenger RNA consists of an inverted 7-methylguanosine linked to the first transcribed nucleotide by a unique 5'-5' triphosphate bond followed by 2'-O-ribose methylation of the first and often the second transcribed nucleotides, likely serving to modify efficiency of transcript processing, translation and stability. Cap2 methylates the ribose of the second transcribed nucleotide. Relationship to other cap-modifying enzymes, overview
the enzyme is involved in formation of the cap 4 structure, a cap structure of the SL RNA unique in eukaryotes with 4 nucleotides after the cap carrying a total of seven methyl groups. Modifications at the +3 and +4 positions are important for binding to the nuclear cap-binding complex, but MT57 is not essential. The Trypanosoma brucei cap binding complex can distinguish between a cap 4 and an m7G structure and it has a much higher affinity for the cap 4 substrate
enzyme Cap2 expression is regulated by Pax6, a key regulator of the entire cascade of ocular lens formation through specific binding to promoters and enhancers of batteries of target genes
enzyme MT48 structural modeling using the VP39 crystal structure as a template, TbMT48 domains involved in S-adenosyl-methionine and cap binding, overview
FTSJD1, the candidate hMTr2, is composed of two RFM domains, sequence comparisons, and has a K-D-K active site. Each residue of the K-D-K triad is essential for the activity of the enzyme
FTSJD1, the candidate hMTr2, is composed of two RFM domains, sequence comparisons, and has a K-D-K active site. Each residue of the K-D-K triad is essential for the activity of the enzyme
structural analysis of human 2'-O-ribose methyltransferases involved in mRNA cap structure formation, homology modeling of the CMTr2 catalytic domain bound to its target using the crystal structure of CMTr1 catalytic domain, overview. CMTr2 is divided into two parts: the amino-terminal part with the catalytic RFM domain (CMTr21-430) and the C-terminal part with the non-catalytic RFM domain (CMTr2430-770). The single domains of CMTr2 do not bind the substrate and do not exhibit any cap MTase activity alone or when mixed together as separately purified chains. Thus, CMTr2 requires both RFM domains in a single polypeptide chain for substrate binding and methylation. Residues K74, L77, W85, T89, K307, H142, and E145 are involved in RNA binding and catalysis, while residues residues S78, H86 and Q113 are not important
structural analysis of human 2'-O-ribose methyltransferases involved in mRNA cap structure formation, homology modeling of the CMTr2 catalytic domain bound to its target using the crystal structure of CMTr1 catalytic domain, overview. CMTr2 is divided into two parts: the amino-terminal part with the catalytic RFM domain (CMTr21-430) and the C-terminal part with the non-catalytic RFM domain (CMTr2430-770). The single domains of CMTr2 do not bind the substrate and do not exhibit any cap MTase activity alone or when mixed together as separately purified chains. Thus, CMTr2 requires both RFM domains in a single polypeptide chain for substrate binding and methylation. Residues K74, L77, W85, T89, K307, H142, and E145 are involved in RNA binding and catalysis, while residues residues S78, H86 and Q113 are not important
CMTr2 is divided into two parts: the amino-terminal part with the catalytic RFM domain (CMTr21-430) and the C-terminal part with the non-catalytic RFM domain (CMTr2430-770). The single domains of CMTr2 do not bind the substrate and do not exhibit any cap MTase activity alone or when mixed together as separately purified chains. Thus, CMTr2 requires both RFM domains in a single polypeptide chain for substrate binding and methylation
CMTr2 is divided into two parts: the amino-terminal part with the catalytic RFM domain (CMTr21-430) and the C-terminal part with the non-catalytic RFM domain (CMTr2430-770). The single domains of CMTr2 do not bind the substrate and do not exhibit any cap MTase activity alone or when mixed together as separately purified chains. Thus, CMTr2 requires both RFM domains in a single polypeptide chain for substrate binding and methylation
genetic ablation of MT57 is compatible with cell viability and leads to the accumulation of SL RNA with a cap structure defective at positions +3 and +4.. Transsplicing utilization of the SL RNA is not detectably affected in mt57-/- cells, analysis of the SL cap structure in mt57-/- cells, overview
silencing of TbMT48 mRNA by RNAi downregulation does not produce a lethal phenotype, as MT48-RNAi trypanosomes remain viable even after 10 days of tetracycline induction, generation of MT48 KO clonal cell lines by homologous recombination with PCR-generated cassettes. An observed defect in cap 4 modification, specific for MT48 ablation, can be complemented by reintroduction of a copy of the MT48 gene into mt48-/- cells
the mt57-/- mutant cells are complemented with the triple MT57 mutant W62D/G63D/Q64D and with MT57 containing the K266A mutation, both mutants do not reestablish the +5 primer extension stop to wild-type levels
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the shRNA-mediated knockdown of transcription factor Pax6 reveals downregulation of a set of direct target genes, including Cap2, Farp1, Pax6, Plekha1, Prox1, Tshz2, and Zfp536