Necessary and sufficient factors for the import of transfer RNA into the kinetoplast mitochondrion

Mukherjee, Saikat; Basu, Sandip K.; Home, Pratik; Dhar, Gunjan; Adhya, Samit

doi:10.1038/embor.2011.94

Cited by 8 publications

(8 citation statements)

References 3 publications

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“…Seven of these proteins were also identified Previous characterization of L. tropica led to the identification of an 11-subunit protein complex, called the RIC, involved in the translocation of tRNAs into the mitochondrion. However, multiple protein components of the Leishmania RIC are subunits of mitochondrial oxidative phosphorylation complexes, including subunits IV and VI of cytochrome c oxidase and the Reiske iron sulfur protein from cytochrome bc1 reductase (22). If these proteins have dual functions in mitochondrial ATP production and tRNA import in Leishmania, it is likely that African trypanosomes use a distinctly different tRNA translocon.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Membrane Complex That Contains Proteins Necessary for tRNA Import in Trypanosoma brucei

Seidman

Johnson

Gerbasi

et al. 2012

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Mitochondrial Membrane Complex That Contains Proteins Necessary for tRNA Import in Trypanosoma brucei

Seidman

Johnson

Gerbasi

et al. 2012

Journal of Biological Chemistry

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“…Applied to mitochondrial import of RNA, this method has been used to search for import signals in RNAs recognized by L. tropica mitochondrial receptors (Bhattacharyya et al 2002). In this protozoan, the whole set of mitochondrial tRNAs is imported from the cytosol by a mechanism that is different from the one found in yeast (Mukherjee et al 2007). A pool of random 16-mer sequences flanked by anchors has been subjected to selection for import into isolated L. tropica mitochondria, and thus permitted identifying a set of short ''import signals'' corresponding to the fragments of different tRNA domains (Bhattacharyya et al 2002.…”

Section: In Organello Selection Of Importable Rna Aptamersmentioning

confidence: 99%

Selection of RNA aptamers imported into yeast and human mitochondria

Kolesnikova¹,

Kazakova²,

Comte³

et al. 2010

RNA

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In the yeast Saccharomyces cerevisiae, nuclear DNA-encoded tRNA Lys CUU is partially imported into mitochondria. We previously found that the synthetic transcripts of yeast tRNA Lys and a number of their mutant versions could be specifically internalized by isolated yeast and human mitochondria. The mitochondrial targeting of tRNA Lys in yeast was shown to depend on the cytosolic precursor of mitochondrial lysyl-tRNA synthetase and the glycolytic enzyme enolase. Here we applied the approach of in vitro selection (SELEX) to broaden the spectrum of importable tRNA-derived molecules. We found that RNAs selected for their import into isolated yeast mitochondria have lost the potential to acquire a classical tRNA-shape. Analysis of conformational rearrangements in the importable RNAs by in-gel fluorescence resonance energy transfer (FRET) approach permitted us to suggest that protein factor binding and subsequent import require formation of an alternative structure, different from a classic L-form tRNA model. We show that in the complex with targeting protein factor, enolase 2, tRK1 adopts a particular conformation characterized by bringing together the 39-end and the TCC loop. This is a first evidence for implication of RNA secondary structure rearrangement in the mechanism of mitochondrial import selectivity. Based on these data, a set of small RNA molecules with significantly improved efficiency of import into yeast and human mitochondria was constructed, opening the possibility of creating a new mitochondrial vector system able to target therapeutic oligoribonucleotides into deficient human mitochondria.

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“…This is interesting for the following reason: it has been claimed that the tRNA import machinery of the mitochondrial inner membrane of Leishmania tropica consists of a protein complex (termed RIC) composed of nine proteins six of which are essential for tRNA import (Bhattacharyya and Adhya, 2004). Three of the essential subunits of RIC are bona fide components of the respiratory chain and therefore are proposed to have a dual function in OXPHOS and mitochondrial tRNA import (Mukherjee et al ., 2007). The orthologues of these three proteins are not detectable in bloodstream forms T. brucei and thus cannot be required for tRNA import.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial translation is essential in bloodstream forms of Trypanosoma brucei

Cristodero

Seebeck

Schneider

2010

Molecular Microbiology

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SummaryThe parasitic protozoa Trypanosoma brucei has a complex life cycle. Oxidative phosphorylation is highly active in the procyclic form but absent from bloodstream cells. The mitochondrial genome encodes several gene products that are required for oxidative phosphorylation, but it completely lacks tRNA genes. For mitochondrial translation to occur, the import of cytosolic tRNAs is therefore essential for procyclic T. brucei. Whether the same is true for the bloodstream form has not been studied so far. Here we show that the steady-state levels of mitochondrial tRNAs are essentially the same in both life stages. Editing of the imported tRNA Trp also occurs in both forms as well as in mitochondria of Trypanosoma evansi, which lacks a genome and a translation system. These results show that mitochondrial tRNA import is a constitutive process that must be mediated by proteins that are expressed in both forms of the life cycle and that are not encoded in the mitochondrial genome. Moreover, bloodstream cells lacking either mitochondria-specific translation elongation factor Tu or mitochondrial tryptophanyl-tRNA synthetase are not viable indicating that mitochondrial translation is also essential in this stage. Both of these proteins show trypanosomatid-specific features and may therefore be excellent novel drug targets.

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Necessary and sufficient factors for the import of transfer RNA into the kinetoplast mitochondrion

Cited by 8 publications

References 3 publications

Mitochondrial Membrane Complex That Contains Proteins Necessary for tRNA Import in Trypanosoma brucei

Mitochondrial Membrane Complex That Contains Proteins Necessary for tRNA Import in Trypanosoma brucei

Selection of RNA aptamers imported into yeast and human mitochondria

Mitochondrial translation is essential in bloodstream forms of Trypanosoma brucei

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