rRNA N6-adenosine-methyltransferase METTL5 (METTL5)

rRNA N6-adenosine-methyltransferase METTL5 (*METTL5*) is an RNA methyltransferase enzyme responsible for installing N6-methyladenosine (m^6A) at position 1832 of 18S ribosomal RNA[1][2][3]. It forms a heterodimeric complex with TRMT112, which stabilizes METTL5 and is required for its enzymatic activity[1]. METTL5 plays a key role in regulating the translation of specific mRNAs, particularly those involved in cell fate determination and differentiation, such as FBXW7 and c-Myc[2][5]. In mouse models, loss of METTL5 impairs neural development and brain function, including learning and memory[4]. METTL5 has been implicated as an oncogene in pancreatic cancer by promoting cell proliferation, migration, invasion, and tumorigenesis, likely through altered translation of c-Myc[5]. The enzyme belongs to the class I SAM-dependent methyltransferase family and is structurally similar to other RNA methyltransferases, such as METTL3 and METTL16, but is specific for rRNA[1]. There are currently no drugs directly targeting METTL5, but its activity and levels may serve as biomarkers in disease contexts. Safety concerns for METTL5-targeted therapies include risks of disrupting protein synthesis or neural development.

Other names

Methyltransferase-like protein 5HSPC133DC3MRT72rRNA N(6)-adenosine-methyltransferase METTL5

Inhibition of methyltransferase activity (potential, but no drugs documented); Indirect modulation of translation via methylation of rRNA, affecting synthesis of proteins such as c-Myc