Poly(A) RNA polymerase, mitochondrial (MTPAP)

Poly(A) RNA polymerase, mitochondrial (MTPAP), is the main enzyme responsible for adding 3′ poly(A) tails to mitochondrial messenger RNA transcripts in mammals[1][3][5]. This polyadenylation is essential for mitochondrial mRNA stability and proper gene expression. MTPAP is a non-canonical poly(A) polymerase, active as a dimer and featuring domains characteristic of the DNA polymerase β family (palm and fingers domains) as well as an N-terminal region that mediates dimerization and RNA binding[1][3]. The enzyme displays a strong preference for ATP as a substrate but can also weakly utilize UTP in vitro[5]. Mutations in MTPAP, most notably the N478D missense mutation, cause severe neurological disorders like autosomal recessive spastic ataxia 4 (SPAX4), primarily via defective mitochondrial mRNA polyadenylation leading to impaired respiratory chain complex expression and progressive neurodegeneration[1][2]. MTPAP functions independently but its activity can be modulated by mitochondrial RNA-binding proteins such as LRPPRC/SLIRP[2]. Currently, there are no known drugs that directly target MTPAP[5], and no therapeutic small molecules are established for this enzyme.

Other names

PAPD1mtPAPTUTase 1TENT6SPAX4Poly(A) RNA polymerase, mitochondrialPAP-associated domain-containing protein 1Polynucleotide adenylyltransferaseTerminal uridylyltransferase 1TUTase1PAP