Activation of trypanosome surface glycoprotein genes involves a duplication-transposition leading to an altered 3′ end

Bernards, André; Lex, H.T.; Ploeg, A. van der; Frasch, Carlos; Borst, Piet; Boothroyd, John C.; Coleman, Sharon Louise; Cross, George A.M.

doi:10.1016/0092-8674(81)90391-3

Cited by 254 publications

(110 citation statements)

References 30 publications

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“…Recombinant DNA Procedures-Genomic DNA was extracted as described previously (22). RNA was obtained using a High Pure RNA Isolation Kit (Roche Applied Science).…”

Section: Methodsmentioning

confidence: 99%

Intracellular Positioning of Isoforms Explains an Unusually Large Adenylate Kinase Gene Family in the Parasite Trypanosoma brucei

Ginger

Ngazoa

Pereira

et al. 2005

Journal of Biological Chemistry

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Adenylate kinases occur classically as cytoplasmic and mitochondrial enzymes, but the expression of seven adenylate kinases in the flagellated protozoan parasite Trypanosoma brucei (order, Kinetoplastida; family, Trypanosomatidae) easily exceeds the number of isoforms previously observed within a single cell and raises questions as to their location and function. We show that a requirement to target adenylate kinase into glycosomes, which are unique kinetoplastid-specific microbodies of the peroxisome class in which many reactions of carbohydrate metabolism are compartmentalized, and two different flagellar structures as well as cytoplasm and mitochondrion explains the expansion of this gene family in trypanosomes. The three isoforms that are selectively built into either the flagellar axoneme or the extra-axonemal paraflagellar rod, which is essential for motility, all contain long N-terminal extensions. Biochemical analysis of the only short form trypanosome adenylate kinase revealed that this enzyme catalyzes phosphotransfer of ␥-phosphate from ATP to AMP, CMP, and UMP acceptors; its high activity and specificity toward CMP is likely to reflect an adaptation to very low intracellular cytidine nucleotide pools. Analysis of some of the phosphotransfer network using RNA interference suggests considerable complexity within the homeostasis of cellular energetics. The anchoring of specific adenylate kinases within two distinct flagellar structures provides a paradigm for metabolic organization and efficiency in other flagellates.

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“…Recombinant DNA Procedures-Genomic DNA was extracted as described previously (22). RNA was obtained using a High Pure RNA Isolation Kit (Roche Applied Science).…”

Section: Methodsmentioning

confidence: 99%

Intracellular Positioning of Isoforms Explains an Unusually Large Adenylate Kinase Gene Family in the Parasite Trypanosoma brucei

Ginger

Ngazoa

Pereira

et al. 2005

Journal of Biological Chemistry

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“…In a few cases, changes in gene expression arise in conjunction with changes in DNA, either in the numbers of genes determining a given character (e.g., rRNA in many organisms, chorion proteins in Drosophila, dihydrofolate reductase in cultured cells) or in their rearrangement (e.g., antibodies in mammals, mating types in yeasts, surface proteins in trypanosomes); see Brown (6) for a review. Changes in the expression of genes controlling the surface proteins of trypanosomes are accompanied by major rearrangements occurring near the 3' end of the gene (3,12,14). By analogy, it has been suggested that the same kind of changes might explain shifts of surface proteins in Paramecium (6).…”

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confidence: 99%

Structure and expression of genes for surface proteins in Paramecium.

et al. 1983

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Surface proteins from 11 antigenic types of Paramecium tetraurelia vary in molecular weight from 251,000 to 308,000. The size of a series of polyadenylated RNAs obtained from these types were correlated with the sizes of the proteins and judged to be the mRNAs for the proteins. The mRNAs were used to identify genomic DNA clones containing complementary sequences. The gene for antigen A was present in one copy per genome, and the data suggest that extensive introns were absent. When restriction enzyme digests of DNA from cultures of paramecia with active and inactive genes were probed with portions of the cloned genes, no evidence for rearrangements or changes in gene dosage was found.

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“…The trypanosome can change the antigenic composition of its surface by switching the VSG gene expressed (see Borst and Cross, 1982). Switching occurs either by a duplicative transposition of an inactive VSG gene to a telomeric expression site (Hoeijmakers et al, 1980;Pays et al, 1981Pays et al, , 1983aBernards et al, 1981;Majiwa et al, 1982;Longacre et al, 1983), or by the activation of a new telomeric site and the inactivation of the old one (Laurent et al, 1984;Pays et al, 1983b;Bernards et al, 1984;Michels et al, 1984;Myler et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

Trypanosoma brucei: a surface antigen mRNA is discontinuously transcribed from two distinct chromosomes.

Guyaux¹,

Cornelissen²,

Pays³

et al. 1985

The EMBO Journal

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Communicated by M.SteinertThe mRNAs for variant surface glycoproteins (VSGs) and many other proteins in Trypanosoma brucei start with the same sequence of 35 nucleotides, encoded by a separate miniexon. There are -200 mini-exon genes per trypanosome and these are highly clustered on large chromosomes. We have found two trypanosome variants that express a VSG gene located on a small, 225-kb chromosome. Each gene yields a mRNA containing the 35-nucleotide sequence even though the 225-kb chromosome does not contain a complete mini-exon gene. These results provide a strong support for the hypothesis that transcription of protein-coding genes in trypanosomes is discontinuous.

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Activation of trypanosome surface glycoprotein genes involves a duplication-transposition leading to an altered 3′ end

Cited by 254 publications

References 30 publications

Intracellular Positioning of Isoforms Explains an Unusually Large Adenylate Kinase Gene Family in the Parasite Trypanosoma brucei

Intracellular Positioning of Isoforms Explains an Unusually Large Adenylate Kinase Gene Family in the Parasite Trypanosoma brucei

Structure and expression of genes for surface proteins in Paramecium.

Trypanosoma brucei: a surface antigen mRNA is discontinuously transcribed from two distinct chromosomes.

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