METTL4
Description
The METTL4 (methyltransferase 4, N6-adenosine) is a protein-coding gene located on chromosome 18.
METTL4 is a methyltransferase that can modify both RNA and DNA. It acts as a N(6)-adenine-specific RNA methyltransferase by catalyzing the formation of N6,2'-O-dimethyladenosine (m6A(m)) on internal positions of U2 small nuclear RNA (snRNA). This methylation regulates RNA splicing. METTL4 can also act as a N(6)-adenine-specific DNA methyltransferase by mediating methylation of DNA on the 6th position of adenine (N(6)-methyladenosine). However, the existence of N(6)-methyladenosine (m6A) on DNA in mammals is unclear and needs further investigation. METTL4 also acts as a regulator of mitochondrial transcript levels and mitochondrial DNA (mtDNA) copy number by mediating mtDNA N(6)-methylation. m6A on mtDNA reduces transcription by repressing TFAM DNA-binding and bending. Finally, METTL4 deposition of N(6)-methyladenosine regulates Polycomb silencing by triggering ubiquitination and degradation of sensor proteins ASXL1 and MPND, leading to inactivation of the PR-DUB complex and subsequent preservation of Polycomb silencing.
METTL4 is also known as HsT661.
Associated Diseases
- hemoglobin D disease
- dominant beta-thalassemia
- hemoglobin E disease
- hemoglobin C-beta-thalassemia syndrome
- hemoglobin H disease
- erythroleukemia, familial, susceptibility to
- overhydrated hereditary stomatocytosis
- hereditary persistence of fetal hemoglobin-sickle cell disease syndrome
- dehydrated hereditary stomatocytosis
- severe congenital hypochromic anemia with ringed sideroblasts
- beta-thalassemia-X-linked thrombocytopenia syndrome
- hemolytic anemia due to diphosphoglycerate mutase deficiency
- combined immunodeficiency due to OX40 deficiency
- hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome
