NSUN2
Function
RNA cytosine C(5)-methyltransferase that methylates cytosine to 5-methylcytosine (m5C) in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs) (PubMed:17071714, PubMed:22995836, PubMed:31199786, PubMed:31358969). Involved in various processes, such as epidermal stem cell differentiation, testis differentiation and maternal to zygotic transition during early development: acts by increasing protein synthesis; cytosine C(5)-methylation promoting tRNA stability and preventing mRNA decay (PubMed:31199786). Methylates cytosine to 5-methylcytosine (m5C) at positions 34 and 48 of intron-containing tRNA(Leu)(CAA) precursors, and at positions 48, 49 and 50 of tRNA(Gly)(GCC) precursors (PubMed:17071714, PubMed:22995836, PubMed:31199786). tRNA methylation is required generation of RNA fragments derived from tRNAs (tRFs) (PubMed:31199786). Also mediates C(5)-methylation of mitochondrial tRNAs (PubMed:31276587). Catalyzes cytosine C(5)-methylation of mRNAs, leading to stabilize them and prevent mRNA decay: mRNA stabilization involves YBX1 that specifically recognizes and binds m5C-modified transcripts (PubMed:22395603, PubMed:31358969, PubMed:34556860). Cytosine C(5)-methylation of mRNAs also regulates mRNA export: methylated transcripts are specifically recognized by THOC4/ALYREF, which mediates mRNA nucleo-cytoplasmic shuttling (PubMed:28418038). Also mediates cytosine C(5)-methylation of non-coding RNAs, such as vault RNAs (vtRNAs), promoting their processing into regulatory small RNAs (PubMed:23871666). Cytosine C(5)-methylation of vtRNA VTRNA1.1 promotes its processing into small-vault RNA4 (svRNA4) and regulates epidermal differentiation (PubMed:31186410). May act downstream of Myc to regulate epidermal cell growth and proliferation (By similarity). Required for proper spindle assembly and chromosome segregation, independently of its methyltransferase activity (PubMed:19596847).
Involvement in disease
Intellectual developmental disorder, autosomal recessive 5
MRT5
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylated at Ser-139 by AURKB during mitosis, leading to abolish methyltransferase activity and the interaction with NPM1.
Sequence Similarities
Belongs to the class I-like SAM-binding methyltransferase superfamily. RsmB/NOP family. TRM4 subfamily.
Tissue Specificity
Expressed in adult and fetal brain and in lymphoblastoid cells.
Cellular localization
- Nucleus
- Nucleolus
- Cytoplasm
- Mitochondrion
- Cytoplasm
- Cytoskeleton
- Spindle
- Secreted
- Extracellular exosome
- Concentrated in the nucleolus during interphase and translocates to the spindle during mitosis as an RNA-protein complex that includes 18S ribosomal RNA (PubMed:19596847). In testis, localizes to the chromatoid body (By similarity).
Alternative names
SAKI, TRM4, NSUN2, RNA cytosine C(5)-methyltransferase NSUN2, Myc-induced SUN domain-containing protein, NOL1/NOP2/Sun domain family member 2, Substrate of AIM1/Aurora kinase B, mRNA cytosine C(5)-methyltransferase, tRNA cytosine C(5)-methyltransferase, tRNA methyltransferase 4 homolog, Misu, hTrm4