Mitochondrial mRNA

Stuart, K., RNA editing in mitochondrial mRNA of trypanoso-matids. Trends Biochem. Sci. 16 68-72, 1991. RNA editing is processing that involves the removal, addition, and modification of nucleotides in the coding regions of nascent transcripts. 

RNA editing. Many uridine molecules are inserted into some mitochondrial mRNAs in trypanosomes. The uridine residues come from the poly(U) tail of a donor strand. Nucleoside triphosphates do not participate in this reaction. Propose a reaction mechanism that accounts for these findings. (Hint Relate RNA editing to RNA splicing.)... 

Since nucleic acids generally cannot go in and out of mitochondria, all mitochondria appear to code for their own rRNAs and tRNAs. For the same reason, only the mRNAs that have been transcribed from the mitochondrial genome are translated in the mitochondria. A unique feature of mitochondrial mRNAs is the lack of a m G cap at the 5 end (reviewed by Bag, 1991). There are only 22-25 tRNA species in the mitochondria, indicating that a single tRNA can recognize more than one codon. There are some structural and sequence differences in the mitochondrial tRNAs. Furthermore, deviations from the standard genetic code, for example, utilization of AUA as the initiation codon instead of AUG, and reading UGA as a tryptophan instead of a stop codon, are a unique feature of mitochondria (Lapointe... 

The promoter sequences recognized by mitochondrial RNA polymerases include the transcription start site. These promoter sequences, which are rich in A residues, have been characterized in the mtDNA from yeast, plants, and animals. The circular, human mitochondrial genome contains two related 15-bp promoter sequences, one for the transcription of each strand. Each strand is transcribed in its entirety the long primary transcripts are then processed to yield mitochondrial mRNAs, rRNAs, and tRNAs. A small basic protein called mtTFl, which binds immediately upstream from the two mitochondrial promoters, greatly stimulates transcription. A homologous protein found in yeast mitochondria is required for maintenance of mtDNA and probably performs a similar function. 

All organisms studied so far use the same genetic code, with some rare exceptions. One exception occurs in human mitochondrial mRNA, where UGA codes for tryptophan instead of serving as a stop codon, AUA codes for methionine instead of isoleucine, and CUA codes for threonine instead of leucine. 

Fig. 15 Effects of interferon-a or -P (IFN-ot/P) rai mitochondrial transcripts. Through its membrane receptor (IFNR), IFN-a/p both induces and activates RNase L. This endonuclease cleaves the mRNA of mitochondrial transcription factor A (TFAM), thus decreasing the TFAM protein and the synthesis of mitochondrial mRNAs (mt-mRNAs). RNase L is also present within mitochondria, where it cleaves the mt-mRNAs. Thmefme, IFN-ot/p decreases both the synthesis and the stability of mitochondrial transraipts...

Le Dinh T, Freneaux E, Labbe G, Letteron P, Degott C, Geneve J, Berson A, Larrey D, Pessayre D (1988) Amineptine, a tricyclic antidepressant, inhibits the mitochondrial oxidation of fatty acids and produces microvesicular steatosis of the liver in mice. J Pharmacol Exp Ther 247 745-750 Le Roy F, Bisbal C, Silhol M, Martinand C, Lebleu B, Salehzada T (2001) The 2-5A/RNase L/RNase inhibitor (RLl) pathway regulates mitochondrial mRNAs stability in interferon-a-treated H9 cells. J Biol Chem 276 48473 8482 Le Roy F, Silhol M, Salehzada T, Bisbal C (2007) Regulation of mitochondrial mRNA stability by RNase L is translation-dependent and controls IFNalpha-induced apoptosis. Cell Death Differ 14 1406-1413... 

Montoya, J., Ojala, D. Attardi, G. (1981) Distinctive Features of the 5 -terminal Sequences of Human Mitochondrial mRNAs , Nature (Lond.), 290, 465-74 Morell, A.G., Irvine, R.A., Stemlieb, I., Scheinberg, H. Ashwell, G. (1968) Physical and Chemical Studies on Ceruloplasmin V. Metabolic Studies on Sialic Acid-free Ceruloplasmin in vivo Journal of Biological Chemistry, 253, 155-9... 

RNA editing A type of RNA processing that has been found in the mitochondrial mRNAs of certain eukaryotes, in which the RNA sequence is altered by the insertion of uridine residues at specific sites. 

Genetic code in mitochondrial mRNA In mitochondrial mRNA, some of the codons are different from those listed in the table, which was established for cytoplasmic and bacterial mRNA. For example, in human mitochondrial mRNA, AGA and AGG are used as termination codons. Other differences are as follows ... 

Two types of mRNA editing are insertional and substitutional editing. Inser-tional editing includes (a) insertion or deletion of one or more U residues [typically in mitochondrial mRNAs such as cytochrome oxidase subunits II (coxll) and III of trypanosomatids (130—132)], (b) insertion of nontemplated C residues [e.g., single C insertion at 54 sites within 528 codons of mitochondrial mRNA for ATP synthetase a subunit of a slime mold, Physarum polycephalum (133)], and (c) insertion of one or more nontemplated G s [in paramyxovirus P mRNAs (134— 136)]. In substitutional editing, templated C is replaced by U (or vice versa) in the mitochondrial mRNAs [e.g., cytochrome c oxidase subunit 2 (cox2) of plants (137-139), chloroplast mRNA (140), and apolipoprotein B mRNA of mammalian cells (141,142). 

Since it appears by now well established that the mitochondrial rRNAs, and at least the bulk of its tRNAs, are distinct from the species found in the cytosol, both in their nature and in their mode of specification by being mitochondrial transcripts (for reviews see introduction), we have recently concentrated our attention on mitochondrial mRNA. This species is, of course, of the greatest interest, not only because of its intrinsic importance to problems of mitochondrial autonomy, but also because the possibility of its nuclear origin and import into the mitochondria has been explicitly raised by several investigators. We have tried to obtain an answer to this question by means of the following paradigm. Three possible models can be envisaged ... 

Some mitochondrial mRNA originates in the nucleus and some is transcribed from mtDNA... 

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