Abstract
The mitochondrial genome of trypanosomes, unlike that of most other eukaryotes, does not appear to encode any tRNAs. Therefore, mitochondrial tRNAs must be either imported into the organelle or created through a novel mitochondrial process, such as RNA editing. Trypanosomal tRNA(Tyr), whose gene contains an 11-nucleotide intron, is present in both the cytosol and the mitochondrion and is encoded by a single-copy nuclear gene. By site-directed mutagenesis, point mutations were introduced into this tRNA gene, and the mutated gene was reintroduced into the trypanosomal nuclear genome by DNA transfection. Expression of the mutant tRNA led to the accumulation of unspliced tRNA(Tyr) (A. Schneider, K. P. McNally, and N. Agabian, J. Biol. Chem. 268:21868-21874, 1993). Cell fractionation revealed that a significant portion of the unspliced mutant tRNA(Tyr) was recovered in the mitochondrial fraction and was resistant to micrococcal nuclease treatment in the intact organelle. Expression of the nuclear integrated, mutated tRNA gene and recovery of its gene product in the mitochondrial fraction directly demonstrated import. In vitro experiments showed that the unspliced mutant tRNA(Tyr), in contrast to the spliced wild-type form, was no longer a substrate for the cognate aminoacyl synthetase. The presence of uncharged tRNA in the mitochondria demonstrated that aminoacylation was not coupled to import.
MeSH Terms
Animals
Base Sequence
Blotting, Northern
Cell Line, Transformed
Cell Nucleus/metabolism
Cytosol/metabolism
Introns
Mitochondria/metabolism
Molecular Sequence Data
Molecular Weight
Mutagenesis, Site-Directed
Oligodeoxyribonucleotides
Point Mutation
RNA Splicing
RNA, Protozoan/biosynthesis,genetics,isolation & purification
RNA, Transfer, Tyr/biosynthesis,genetics,isolation & purification
Transfection
Trypanosoma brucei brucei/genetics,metabolism
Chemicals
Oligodeoxyribonucleotides
RNA, Protozoan
RNA, Transfer, Tyr
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Schneider A
Intercampus Program in Molecular Parasitology, University of California, San Francisco.
Martin J
Agabian N
References (24)
24 references, click to expand
-
The mitochondrial and cytoplasmic valyl tRNA synthetases in Tetrahymena are indistinguishable.
Arch Biochem Biophys. 1978 Dec;191(2):437-43
PMID: 105668
-
Aminoacylation of tRNA-Leu species from Escherichia coli and from the cytoplasm, chloroplasts and mitochondria of Phaseolus vulgaris by homologous and heterologous enzymes.
Biochim Biophys Acta. 1975 Jan 6;378(1):64-72
PMID: 1091292
-
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
Anal Biochem. 1987 Apr;162(1):156-9
PMID: 2440339
-
The subnuclear localization of tRNA ligase in yeast.
J Cell Biol. 1987 Oct;105(4):1515-26
PMID: 3312232
-
DNA-protein conjugates can enter mitochondria via the protein import pathway.
Nature. 1989 Mar 9;338(6211):170-2
PMID: 2918937
-
Trafficking in small mitochondrial RNA molecules.
Trends Genet. 1989 Mar;5(3):67-9
PMID: 2472029
-
Kinetoplastid mitochondria contain functional tRNAs which are encoded in nuclear DNA and also contain small minicircle and maxicircle transcripts of unknown function.
Nucleic Acids Res. 1989 Jul 25;17(14):5427-45
PMID: 2762144
-
Addition of uridines to edited RNAs in trypanosome mitochondria occurs independently of transcription.
J Biol Chem. 1990 Jul 5;265(19):11368-76
PMID: 1694178
-
The mitochondrial tRNAs of Trypanosoma brucei are nuclear encoded.
J Biol Chem. 1990 Nov 5;265(31):19208-15
PMID: 2229071
-
Targeted insertion of the neomycin phosphotransferase gene into the tubulin gene cluster of Trypanosoma brucei.
Nature. 1990 Nov 8;348(6297):174-5
PMID: 2172836
-
RNA editing--a novel genetic phenomenon?
Science. 1990 Oct 26;250(4980):512-3
PMID: 1700474
-
RNA editing fixes problems in plant mitochondrial transcripts.
Trends Genet. 1991 Feb;7(2):37-9
PMID: 1709762
-
tRNAs of Trypanosoma brucei. Unusual gene organization and mitochondrial importation.
J Biol Chem. 1991 Sep 25;266(27):18313-7
PMID: 1717447
-
Homologous recombination in the tandem calmodulin genes of Trypanosoma brucei yields multiple products: compensation for deleterious deletions by gene amplification.
Genes Dev. 1991 Nov;5(11):2024-32
PMID: 1936992
-
Mitochondrially-imported cytoplasmic tRNA(Lys)(CUU) of Saccharomyces cerevisiae: in vivo and in vitro targetting systems.
Nucleic Acids Res. 1992 Mar 25;20(6):1277-81
PMID: 1561084
-
In vivo import of a normal or mutagenized heterologous transfer RNA into the mitochondria of transgenic plants: towards novel ways of influencing mitochondrial gene expression?
EMBO J. 1992 Apr;11(4):1291-6
PMID: 1563345
-
Identification of nuclear encoded precursor tRNAs within the mitochondrion of Trypanosoma brucei.
J Biol Chem. 1992 Nov 25;267(33):23963-71
PMID: 1385429
-
Nuclear-encoded transfer RNAs in plant mitochondria.
Annu Rev Cell Biol. 1992;8:115-31
PMID: 1476798
-
Editing of transfer RNAs in Acanthamoeba castellanii mitochondria.
Science. 1993 Feb 5;259(5096):812-6
PMID: 8430334
-
Selective import of nuclear-encoded tRNAs into mitochondria of the protozoan Leishmania tarentolae.
Mol Biochem Parasitol. 1993 Apr;58(2):233-45
PMID: 8479448
-
Autonomously replicating single-copy episomes in Trypanosoma brucei show unusual stability.
EMBO J. 1993 Jun;12(6):2529-38
PMID: 8508776
-
Splicing and 3'-processing of the tyrosine tRNA of Trypanosoma brucei.
J Biol Chem. 1993 Oct 15;268(29):21868-74
PMID: 8408041
-
Isolation of kinetoplast-mitochondrial complexes from Leishmania tarentolae.
J Protozool. 1974 Nov;21(5):782-90
PMID: 4217377
-
Import of nuclear deoxyribonucleic acid coded lysine-accepting transfer ribonucleic acid (anticodon C-U-U) into yeast mitochondria.
Biochemistry. 1979 Oct 16;18(21):4600-5
PMID: 387075