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布氏锥虫的变异抗原基因:剪接前导序列孤儿基因的基因组改变及分化过程中表达相关拷贝的保留

Variant antigen genes of Trypanosoma brucei: genomic alteration of a spliced leader orphon and retention of expression-linked copies during differentiation.

作者信息

Parsons M, Nelson R G, Stuart K, Agabian N

出版信息

Proc Natl Acad Sci U S A. 1984 Feb;81(3):684-8. doi: 10.1073/pnas.81.3.684.

DOI:10.1073/pnas.81.3.684
PMID:6322164
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC344899/
Abstract

Variant surface glycoprotein (VSG) gene expression in Trypanosoma brucei involves not only the sequential activation of individual VSG genes during mammalian bloodstream stage antigenic variation but also the regulation of gene expression during cyclic transmission through alternate mammalian and insect hosts. In the bloodstream stage, transcriptional activation of many VSG genes is correlated with the appearance of an additional copy of the gene in a novel genomic location, the expression-linked copy. The parasite loses the ability to synthesize VSG during differentiation from mammalian bloodstream to insect procyclic stage. Five different bloodstream populations were individually converted to procyclic forms. In each case, the procyclic cells retained the expression-linked copy of the bloodstream parent, and it remained in the same immediate genomic context. Transcripts homologous to the VSG structural gene exon were found in bloodstream stage RNA but not in procyclic RNA. Nevertheless, transcripts containing sequences homologous to the VSG mRNA spliced leader were abundant in both procyclic and bloodstream stage cells. When the genomic organization of sequences homologous to the VSG leader was examined, a specific alteration correlated with procylic differentiation was found. These data are discussed in light of biological studies on antigenic variation.

摘要

布氏锥虫中的变异表面糖蛋白(VSG)基因表达不仅涉及哺乳动物血流阶段抗原变异期间单个VSG基因的顺序激活,还涉及通过交替的哺乳动物和昆虫宿主进行循环传播期间的基因表达调控。在血流阶段,许多VSG基因的转录激活与该基因在一个新的基因组位置(表达关联拷贝)出现额外拷贝相关。寄生虫在从哺乳动物血流阶段分化为昆虫前循环阶段时失去合成VSG的能力。五个不同的血流群体分别被转化为前循环形式。在每种情况下,前循环细胞保留了血流亲本的表达关联拷贝,并且它仍处于相同的直接基因组环境中。与VSG结构基因外显子同源的转录本在血流阶段RNA中被发现,但在前循环RNA中未被发现。然而,含有与VSG mRNA剪接前导序列同源序列的转录本在循环前和血流阶段细胞中都很丰富。当检查与VSG前导序列同源的序列的基因组组织时,发现了与前循环分化相关的特定改变。根据关于抗原变异的生物学研究对这些数据进行了讨论。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/161f/344899/7819bc4b45bb/pnas00604-0046-a.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/161f/344899/1807d8eb5baf/pnas00604-0044-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/161f/344899/e421fb837b7f/pnas00604-0044-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/161f/344899/dbad2365aaf8/pnas00604-0044-d.jpg
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Variant antigen genes of Trypanosoma brucei: genomic alteration of a spliced leader orphon and retention of expression-linked copies during differentiation.布氏锥虫的变异抗原基因:剪接前导序列孤儿基因的基因组改变及分化过程中表达相关拷贝的保留
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Sequences homologous to the variant antigen mRNA spliced leader are located in tandem repeats and variable orphons in trypanosoma brucei.与变异抗原mRNA剪接前导序列同源的序列位于布氏锥虫的串联重复序列和可变孤儿基因中。
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A novel DNA nucleotide in Trypanosoma brucei only present in the mammalian phase of the life-cycle.一种仅存在于布氏锥虫生命周期哺乳动物阶段的新型DNA核苷酸。
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引用本文的文献

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Characterization of the 1.35 kilobase DNA repeat unit containing the conserved 35 nucleotides at the 5'-termini of variable surface glycoprotein mRNAs in Trypanosoma brucei.布氏锥虫可变表面糖蛋白mRNA 5'末端含保守35个核苷酸的1.35千碱基DNA重复单元的特征分析
Nucleic Acids Res. 1984 Jun 25;12(12):4907-20. doi: 10.1093/nar/12.12.4907.
2
Identification of a small RNA containing the trypanosome spliced leader: a donor of shared 5' sequences of trypanosomatid mRNAs?一种含有锥虫剪接前导序列的小RNA的鉴定:锥虫mRNA共享5'序列的供体?
Cell. 1984 Oct;38(3):721-9. doi: 10.1016/0092-8674(84)90267-8.
3
Trypanosome mRNAs share a common 5' spliced leader sequence.

本文引用的文献

1
In vitro cultivation of pleomorphic Trypanosoma brucei stocks: a possible source of variable antigens for immunization studies.多形布氏锥虫株的体外培养:免疫研究中可变抗原的一个可能来源。
Trans R Soc Trop Med Hyg. 1981;75(1):150-1. doi: 10.1016/0035-9203(81)90050-x.
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The expression-linked copy of a surface antigen gene in Trypanosoma is probably the one transcribed.锥虫表面抗原基因的表达相关拷贝可能是被转录的那个。
Nature. 1981 Jul 16;292(5820):265-7. doi: 10.1038/292265a0.
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Transcripts coding for variant surface glycoproteins of Trypanosoma brucei have a short, identical exon at their 5' end.
锥虫mRNA共享一个共同的5'剪接前导序列。
Cell. 1984 Aug;38(1):309-16. doi: 10.1016/0092-8674(84)90552-x.
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Possible DNA modification in GC dinucleotides of Trypanosoma brucei telomeric sequences; relationship with antigen gene transcription.
Nucleic Acids Res. 1984 Jul 11;12(13):5235-47. doi: 10.1093/nar/12.13.5235.
5
The IsTat 1.3 VSG multigene family in Trypanosoma brucei: retention of the expression linked copy through multiple antigenic switches.布氏锥虫中的IsTat 1.3 VSG多基因家族:通过多次抗原转换保留表达相关拷贝
Nucleic Acids Res. 1984 Dec 11;12(23):9051-66. doi: 10.1093/nar/12.23.9051.
6
Structure and transcription of a telomeric surface antigen gene of Trypanosoma brucei.布氏锥虫端粒表面抗原基因的结构与转录
Mol Cell Biol. 1985 Mar;5(3):545-53. doi: 10.1128/mcb.5.3.545-553.1985.
7
Calmodulin genes in trypanosomes are tandemly repeated and produce multiple mRNAs with a common 5' leader sequence.锥虫中的钙调蛋白基因串联重复,并产生具有共同5'前导序列的多个mRNA。
Proc Natl Acad Sci U S A. 1985 Jun;82(12):3998-4002. doi: 10.1073/pnas.82.12.3998.
8
Trypanosoma brucei: a surface antigen mRNA is discontinuously transcribed from two distinct chromosomes.布氏锥虫:一种表面抗原mRNA由两条不同的染色体间断转录产生。
EMBO J. 1985 Apr;4(4):995-8. doi: 10.1002/j.1460-2075.1985.tb03729.x.
9
A 5' spliced leader is added in trans to both alpha- and beta-tubulin transcripts in Trypanosoma brucei.在布氏锥虫中,一个5'剪接前导序列以反式方式添加到α-微管蛋白和β-微管蛋白转录本上。
Proc Natl Acad Sci U S A. 1985 Sep;82(17):5695-9. doi: 10.1073/pnas.82.17.5695.
10
Inactivation and reactivation of a variant-specific antigen gene in cyclically transmitted Trypanosoma brucei.循环传播的布氏锥虫中变异特异性抗原基因的失活与重新激活
EMBO J. 1985 Apr;4(4):989-93. doi: 10.1002/j.1460-2075.1985.tb03728.x.
编码布氏锥虫可变表面糖蛋白的转录本在其5'端有一个短的、相同的外显子。
Gene. 1982 Dec;20(2):281-9. doi: 10.1016/0378-1119(82)90046-4.
4
Genomic environment of the expression-linked extra copies of genes for surface antigens of Trypanosoma brucei resembles the end of a chromosome.布氏锥虫表面抗原基因表达相关额外拷贝的基因组环境类似于染色体末端。
Nature. 1982 Sep 30;299(5882):451-3. doi: 10.1038/299451a0.
5
Genomic environment of T. brucei VSG genes: presence of a minichromosome.布氏锥虫VSG基因的基因组环境:微型染色体的存在
Nature. 1982 Sep 30;299(5882):417-21. doi: 10.1038/299417a0.
6
Molecular basis for trypanosome antigenic variation.锥虫抗原变异的分子基础。
Cell. 1982 Jun;29(2):291-303. doi: 10.1016/0092-8674(82)90146-5.
7
Genomic organization of Trypanosoma brucei variant antigen gene families in sequential parasitemias.布氏锥虫可变抗原基因家族在连续虫血症中的基因组组织
Mol Biochem Parasitol. 1983 Nov;9(3):255-69. doi: 10.1016/0166-6851(83)90101-9.
8
Molecular characterization of initial variants from the IsTat I serodeme of Trypanosoma brucei.布氏锥虫IsTat I血清型初始变体的分子特征分析
Mol Biochem Parasitol. 1983 Nov;9(3):241-54. doi: 10.1016/0166-6851(83)90100-7.
9
Sequences homologous to the variant antigen mRNA spliced leader are located in tandem repeats and variable orphons in trypanosoma brucei.与变异抗原mRNA剪接前导序列同源的序列位于布氏锥虫的串联重复序列和可变孤儿基因中。
Cell. 1983 Oct;34(3):901-9. doi: 10.1016/0092-8674(83)90547-0.
10
The transposition unit of variant surface glycoprotein gene 118 of Trypanosoma brucei. Presence of repeated elements at its border and absence of promoter-associated sequences.布氏锥虫可变表面糖蛋白基因118的转座单元。其边界处存在重复元件且缺乏启动子相关序列。
J Mol Biol. 1983 Jun 15;167(1):57-75. doi: 10.1016/s0022-2836(83)80034-5.