NSUN2

This gene encodes a methyltransferase that catalyzes the methylation of cytosine to 5-methylcytosine (m5C) at position 34 of intron-containing tRNA(Leu)(CAA) precursors. This modification is necessary to stabilize the anticodon-codon pairing and correctly translate the mRNA. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.

Full Name

NOP2/Sun RNA Methyltransferase Family Member 2

Function

RNA cytosine C5-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:31358969, PubMed:31199786).
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 C5-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 C5-methylation of mitochondrial tRNAs (PubMed:31276587).
Catalyzes cytosine C5-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 C5-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 C5-methylation of non-coding RNAs, such as vault RNAs (vtRNAs), promoting their processing into regulatory small RNAs (PubMed:23871666).
Cytosine C5-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).

Biological Process

Cell divisionIEA:UniProtKB-KW
Hair follicle maturationISS:UniProtKB
In utero embryonic developmentIEA:Ensembl
Meiotic cell cycle checkpoint signalingIEA:Ensembl
mRNA methylationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of mRNA export from nucleusManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of stem cell differentiationISS:UniProtKB
RNA methylationManual Assertion Based On ExperimentIBA:GO_Central
Spermatid developmentIEA:Ensembl
tRNA methylationManual Assertion Based On ExperimentIDA:UniProtKB
tRNA modificationTAS:Reactome
tRNA stabilizationISS:UniProtKB

Cellular Location

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).

Involvement in disease

Mental retardation, 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.

PTM

Phosphorylated at Ser-139 by AURKB during mitosis, leading to abolish methyltransferase activity and the interaction with NPM1.