Mitochondrial poly(A) polymerase and polyadenylation

Abstract

Polyadenylation of mitochondrial RNAs in higher eukaryotic organisms have diverse effects on their function and metabolism. Polyadenylation completes the UAA stop codon of a majority of mitochondrial mRNAs in mammals, regulates the translation of the mRNAs, and has diverse effects on their stability. In contrast, polyadenylation of most mitochondrial mRNAs in plants leads to their degradation, consistent with the bacterial origin of this organelle. PAPD1 (mtPAP, TUTase1), a noncanonical poly(A) polymerase (ncPAP), is responsible for producing the poly(A) tails in mammalian mitochondria. The crystal structure of human PAPD1 was reported recently, offering molecular insights into its catalysis. This article is part of a Special Issue entitled: Mitochondrial Gene Expression.

Figure 1

Diverse effects of mitochondrial polyadenylation in higher eukaryotes. Yeast mitochondrial mRNAs are not polyadenylated. Instead, their stability is controlled by a dodecamer sequence at the 3′-end.

Figure 2

Schematic drawing of the domain organization of yeast canonical PAP and human PAPD1, a noncanonical PAP (ncPAP). The palm and fingers domains are shown in yellow and magenta, respectively. The RBD of yeast PAP is shown in cyan. The mitochondrial targeting sequence and RL domain of PAPD1 are shown in black and blue, respectively.

Figure 3

Structural comparisons of PAPD1 with other PAPs and TUTases. (A). Schematic drawing of the structure of yeast PAP (D154A mutant) in complex with ATP and oligoadenylate [56], colored as in Fig. 2. ATP is shown in a cpk model, and the oligo(A) in a stick model. The divalent metal ion is shown as a sphere in orange. (B). Structure of human PAPD1 monomer [21]. (C). Yeast Trf4 in complex with a fragment of Air2 (in orange) [64]. (D). T. brucei MEAT1 in complex with UTP [65]. The bridging domain (BD) is colored in green. (E). T. brucei RNA-editing TUTase2 in complex with UTP [66]. The middle domain (MD) is colored in green. (F). T. brucei TUTase4 in complex with dinucleotide, UpU [68]. The palm and fingers domains of each structure are shown in the same orientation. (G). Structure of human PAPD1 dimer [21]. All structure figures were produced with PyMOL (http://www.pymol.org).