The Trypanosoma brucei MitoCarta and its regulation and splicing pattern during development

Zhang, Xiaobai; Cui, Juan; Nilsson, Daniel; Gunasekera, Kapila; Chanfon, Astrid; Song, Xiaofeng; Wang, Huinan; Xu, Ying; Ochsenreiter, Torsten

doi:10.1093/nar/gkq618

Cited by 56 publications

(54 citation statements)

References 67 publications

(95 reference statements)

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“…Algorithmic prediction programs [Phobius (38) or transmembrane prediction using hidden Markov models predictor (39)] suggested that the translated protein, named "TbCls," contains two C-terminal transmembrane domains and may be targeted to mitochondria (according to MitoCarta predictor) (40). Similar to bacterial-type Cls, TbCls contains two highly conserved H(X)K (X) 4 D motifs found in the active sites of PLD, nucleases, and pox envelope proteins (24).…”

Section: Resultsmentioning

confidence: 99%

An essential bacterial-type cardiolipin synthase mediates cardiolipin formation in a eukaryote

Serricchio

Bütikofer

2012

Proc. Natl. Acad. Sci. U.S.A.

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Cardiolipin is important for bacterial and mitochondrial stability and function. The final step in cardiolipin biosynthesis is catalyzed by cardiolipin synthase and differs mechanistically between prokaryotes and eukaryotes. To study the importance of cardiolipin synthesis for mitochondrial integrity, membrane protein complex formation, and cell proliferation in the human and animal pathogenic protozoan parasite, Trypanosoma brucei , we generated conditional cardiolipin synthase-knockout parasites. We found that cardiolipin formation in T. brucei procyclic forms is catalyzed by a bacterial-type cardiolipin synthase, providing experimental evidence for a prokaryotic-type cardiolipin synthase in a eukaryotic organism. Ablation of enzyme expression resulted in inhibition of de novo cardiolipin synthesis, reduction in cellular cardiolipin levels, alterations in mitochondrial morphology and function, and parasite death in culture. By using immunofluorescence microscopy and blue-native gel electrophoresis, cardiolipin synthase was shown to colocalize with inner mitochondrial membrane proteins and to be part of a large protein complex. During depletion of cardiolipin synthase, the levels of cytochrome oxidase subunit IV and cytochrome c1, reflecting mitochondrial respiratory complexes IV and III, respectively, decreased progressively.

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Section: Resultsmentioning

confidence: 99%

An essential bacterial-type cardiolipin synthase mediates cardiolipin formation in a eukaryote

Serricchio

Bütikofer

2012

Proc. Natl. Acad. Sci. U.S.A.

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“…With the exception of the 47.5-kDa protein, all the co-purifying proteins are essential in one or more life stages of the trypanosome (Table 1) based on high-throughput RNAi analysis (Alsford et al 2011). The 17.9-kDa hypothetical protein has a predicted mitochondrial location (Zhang et al 2010), however it was associated consistently with TbE5 and TbG2 in reciprocal purifications. The association of TbE5 in a complex with a protein predicted to have enzymatic activities involved in two of the three steps of mRNA cap formation is a compelling argument for the involvement of TbE5 in mRNA metabolism, and hence the regulation of translation, opening a multitude of new questions.…”

Section: Rna-binding and Cap 0 Maturation Domains Identified In Tbeifmentioning

confidence: 99%

eIF4F-like complexes formed by cap-binding homolog TbEIF4E5 with TbEIF4G1 or TbEIF4G2 are implicated in post-transcriptional regulation in Trypanosoma brucei

Freire

Vashisht

Malvezzi

et al. 2014

RNA

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Members of the eIF4E mRNA cap-binding family are involved in translation and the modulation of transcript availability in other systems as part of a three-component complex including eIF4G and eIF4A. The kinetoplastids possess four described eIF4E and five eIF4G homologs. We have identified two new eIF4E family proteins in Trypanosoma brucei, and define distinct complexes associated with the fifth member, TbEIF4E5. The cytosolic TbEIF4E5 protein binds cap 0 in vitro. TbEIF4E5 was found in association with two of the five TbEIF4Gs. TbIF4EG1 bound TbEIF4E5, a 47.5-kDa protein with two RNA-binding domains, and either the regulatory protein 14-3-3 II or a 117.5-kDa protein with guanylyltransferase and methyltransferase domains in a potentially dynamic interaction. The TbEIF4G2/TbEIF4E5 complex was associated with a 17.9-kDa hypothetical protein and both 14-3-3 variants I and II. Knockdown of TbEIF4E5 resulted in the loss of productive cell movement, as evidenced by the inability of the cells to remain in suspension in liquid culture and the loss of social motility on semisolid plating medium, as well as a minor reduction of translation. Cells appeared lethargic, as opposed to compromised in flagellar function per se. The minimal use of transcriptional control in kinetoplastids requires these organisms to implement downstream mechanisms to regulate gene expression, and the TbEIF4E5/TbEIF4G1/117.5-kDa complex in particular may be a key player in that process. We suggest that a pathway involved in cell motility is affected, directly or indirectly, by one of the TbEIF4E5 complexes.

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“…KREPB9 had a weaker signal than KREPB10, possibly implying a smaller amount of protein. KREPB9 was previously reported to have mitochondrial localization using a green fluorescent protein (GFP) fusion protein (53). Thus, both KREPB9 and KREPB10 are mitochondrial proteins.…”

Section: Identification Of Krepb9 and Krepb10 Krepb9 And Krepb10mentioning

confidence: 99%

Editosome Accessory Factors KREPB9 and KREPB10 in Trypanosoma brucei

et al. 2012

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bMultiprotein complexes, called editosomes, catalyze the uridine insertion and deletion RNA editing that forms translatable mitochondrial mRNAs in kinetoplastid parasites. We have identified here two new U1-like zinc finger proteins that associate with editosomes and have shown that they are related to KREPB6, KREPB7, and KREPB8, and thus we have named them Kinetoplastid RNA Editing Proteins, KREPB9 and KREPB10. They are conserved and syntenic in trypanosomatids although KREPB10 is absent in Trypanosoma vivax and both are absent in Leishmania. Tandem affinity purification (TAP)-tagged KREPB9 and KREPB10 incorporate into ϳ20S editosomes and/or subcomplexes thereof and preferentially associate with deletion subcomplexes, as do KREPB6, KREPB7, and KREPB8. KREPB10 also associates with editosomes that are isolated via a chimeric endonuclease, KREN1 in KREPB8 RNA interference (RNAi) cells, or MEAT1. The purified complexes have precleaved editing activities and endonuclease cleavage activity that appears to leave a 5= OH on the 3= product. RNAi knockdowns did not affect growth but resulted in relative reductions of both edited and unedited mitochondrial mRNAs. The similarity of KREPB9 and KREPB10 to KREPB6, KREPB7, and KREPB8 suggests they may be accessory factors that affect editing endonuclease activity and as a consequence may affect mitochondrial mRNA stability. KREPB9 and KREPB10, along with KREPB6, KREPB7, and KREPB8, may enable the endonucleases to discriminate among and accurately cleave hundreds of different editing sites and may be involved in the control of differential editing during the life cycle of T. brucei.

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The Trypanosoma brucei MitoCarta and its regulation and splicing pattern during development

Cited by 56 publications

References 67 publications

An essential bacterial-type cardiolipin synthase mediates cardiolipin formation in a eukaryote

An essential bacterial-type cardiolipin synthase mediates cardiolipin formation in a eukaryote

eIF4F-like complexes formed by cap-binding homolog TbEIF4E5 with TbEIF4G1 or TbEIF4G2 are implicated in post-transcriptional regulation in Trypanosoma brucei

Editosome Accessory Factors KREPB9 and KREPB10 in Trypanosoma brucei

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