Polyadenylation and degradation of RNA in the mitochondria Shiri Levy* and Gadi Schuster Faculty of Biology, Technion — Israel Institute of Technology, Haifa 32000, Israel Correspondence: Gadi Schuster (gadis@tx.technion.ac.il) Mitochondria have their own gene expression machinery and the relative abundance of RNA products in these organelles in animals is mostly dictated by their rate of degradation. The molecular mechanisms regulating the differential accumulation of the transcripts in this organelle remain largely elusive. Here, we summarize the present knowledge of how RNA is degraded in human mitochondria and describe the coexistence of stable poly(A) tails and the nonabundant tails, which have been suggested to play a role in the RNA degrad- ation process. Gene expression in human mitochondria Mitochondria are critical for many metabolic pathways, including in the production of ATP via oxida- tive phosphorylation. The organelle is an evolutionary remnant of an endosymbiotic event that occurred between an α-proteobacterium and an ancient host cell 1.5 billion years ago, after which, most of the bacterial genes were transferred to the nuclear genome of the ancient host [1,2]. The mammalian mitochondrial genome preserved a total of 37 genes, encoding 2 ribosomal RNAs, 22 tRNA, and 13 proteins, all of which are oxidative phosphorylation component subunits, essential in several critical metabolic pathways and in maintaining cell viability [3,4]. Mitochondrial RNAs are transcribed from the mitochondrial DNA, as polycistronic molecules, in a process in which the mRNAs and rRNAs are mostly punctuated by tRNAs [3–5]. Endonucleolytic cleavage of tRNAs, at both 5 0 - and 3 0 -ends, is driven by RNase P and RNase Z, respectively, producing, in addition to pro- cessed tRNAs, the rRNA and mRNA transcripts (Figure 1)[5–9]. The released mRNA species are then decorated with stable poly(A) tails and translated by mitochondrial ribosomes. Owing to mito- chondrial genome reduction that evolved with time, 7 of the 13 mRNA molecules contain truncated translational stop codons, composed of only U or UA instead of UAA; therefore, posttranscriptional addition of a stable poly(A) tail at the 3 0 -end of the molecule is required for the production of a func- tional stop codon [10](Figure 1). Additional functions of the stable poly(A) tails were also proposed [11–14]. Aside from the addition of a stable poly(A) tail at the 3 0 -end, the addition of transient and unstable poly(A) tails at the 3 0 -end of truncated transcripts has also been observed [15]. These tails may indicate the polyadenylation-assisted degradation pathway of RNA described in bacteria, archaea, organelles, as well as in the nucleus and cytosol [10,16–18]. Although produced from only a few poly- cistronic transcripts, the rRNA, tRNA, and mRNA transcripts accumulate in the mitochondria to varying concentrations, indicating the importance of a modulated and well-controlled RNA degrad- ation mechanism [19]. The presence of RNA granules, associated with RNA-binding proteins and enzymes that are functionally linked to mitochondrial transcript processing and degradation, has been recently described [20–23]. Mitochondrial ribonucleases To better understand defects in mitochondrial RNA turnover and consequential mitochondrial disorders, extensive investigations to identify the ribonucleases responsible for mitochondrial transcript processing and degradation are underway [3,4]. The mitochondrial RNase P and RNase Z (ELAC2), which process the tRNAs, have been characterized [6–8]. Owing to the established role of polynucleotide phosphorylase *Present address: Department of Biochemistry, University of Washington, Seattle, WA, USA. Version of Record published: 19 October 2016 Received: 25 May 2016 Revised: 24 June 2016 Accepted: 28 June 2016 © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society 1475 Biochemical Society Transactions (2016) 44 1475–1482 DOI: 10.1042/BST20160126 Downloaded from https://portlandpress.com/biochemsoctrans/article-pdf/44/5/1475/431649/bst-2016-0126.pdf by guest on 31 May 2020