• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

全基因组RNA干扰筛选鉴定出布氏锥虫中传播阶段富集基因家族和细胞类型分化的一个调控因子。

Genome-wide RNAi selection identifies a regulator of transmission stage-enriched gene families and cell-type differentiation in Trypanosoma brucei.

作者信息

Rico Eva, Ivens Alasdair, Glover Lucy, Horn David, Matthews Keith R

机构信息

Centre for Immunity, Infection and Evolution, Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, Scotland, United Kingdom.

The Wellcome Trust Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom.

出版信息

PLoS Pathog. 2017 Mar 23;13(3):e1006279. doi: 10.1371/journal.ppat.1006279. eCollection 2017 Mar.

DOI:10.1371/journal.ppat.1006279
PMID:28334017
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5380359/
Abstract

Trypanosoma brucei, causing African sleeping-sickness, exploits quorum-sensing (QS) to generate the 'stumpy forms' necessary for the parasite's transmission to tsetse-flies. These quiescent cells are generated by differentiation in the bloodstream from proliferative slender forms. Using genome-wide RNAi selection we screened for repressors of transmission stage-enriched mRNAs in slender forms, using the stumpy-elevated ESAG9 transcript as a model. This identified REG9.1, whose RNAi-silencing alleviated ESAG9 repression in slender forms and tsetse-midgut procyclic forms. Interestingly, trypanosome surface protein Family 5 and Family 7 mRNAs were also elevated, which, like ESAG9, are T. brucei specific and stumpy-enriched. We suggest these contribute to the distinct transmission biology and vector tropism of T. brucei from other African trypanosome species. As well as surface family regulation, REG9.1-depletion generated QS-independent development to stumpy forms in vivo, whereas REG9.1 overexpression in bloodstream forms potentiated spontaneous differentiation to procyclic forms in the absence of an external signal. Combined, this identifies REG9.1 as a regulator of developmental cell fate, controlling the expression of Trypanosoma brucei-specific molecules elevated during transmission.

摘要

导致非洲昏睡病的布氏锥虫利用群体感应（QS）来产生寄生虫传播至采采蝇所需的“粗短型”。这些静止细胞是由血流中增殖性细长型细胞分化产生的。我们利用全基因组RNA干扰筛选，以粗短型中升高的ESAG9转录本为模型，筛选细长型中传播阶段富集mRNA的抑制因子。这鉴定出了REG9.1，其RNA干扰沉默减轻了细长型和采采蝇中肠前循环型中ESAG9的抑制。有趣的是，锥虫表面蛋白家族5和家族7的mRNA也升高了，它们与ESAG9一样，是布氏锥虫特有的且在粗短型中富集。我们认为这些有助于布氏锥虫与其他非洲锥虫物种在传播生物学和媒介嗜性方面的差异。除了表面家族调控外，REG9.1缺失在体内产生了不依赖群体感应的向粗短型的发育，而血流型中REG9.1的过表达在没有外部信号的情况下增强了向前循环型的自发分化。综合来看，这确定REG9.1是发育细胞命运的调节因子，控制着布氏锥虫在传播过程中升高的特异性分子的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9817/5380359/3516bc5b7933/ppat.1006279.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9817/5380359/803fa187de2e/ppat.1006279.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9817/5380359/f4d238defd8d/ppat.1006279.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9817/5380359/aaff259c0a3f/ppat.1006279.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9817/5380359/84c4780bd317/ppat.1006279.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9817/5380359/3649cd4b6545/ppat.1006279.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9817/5380359/e56dd9f2f289/ppat.1006279.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9817/5380359/76350b0e6e8b/ppat.1006279.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9817/5380359/450fed7288c9/ppat.1006279.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9817/5380359/3516bc5b7933/ppat.1006279.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9817/5380359/803fa187de2e/ppat.1006279.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9817/5380359/f4d238defd8d/ppat.1006279.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9817/5380359/aaff259c0a3f/ppat.1006279.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9817/5380359/84c4780bd317/ppat.1006279.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9817/5380359/3649cd4b6545/ppat.1006279.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9817/5380359/e56dd9f2f289/ppat.1006279.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9817/5380359/76350b0e6e8b/ppat.1006279.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9817/5380359/450fed7288c9/ppat.1006279.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9817/5380359/3516bc5b7933/ppat.1006279.g009.jpg

相似文献

1
Genome-wide RNAi selection identifies a regulator of transmission stage-enriched gene families and cell-type differentiation in Trypanosoma brucei.全基因组RNA干扰筛选鉴定出布氏锥虫中传播阶段富集基因家族和细胞类型分化的一个调控因子。
PLoS Pathog. 2017 Mar 23;13(3):e1006279. doi: 10.1371/journal.ppat.1006279. eCollection 2017 Mar.
2
Interspecies quorum sensing in co-infections can manipulate trypanosome transmission potential.种间群体感应在共感染中可以操纵锥虫的传播潜力。
Nat Microbiol. 2017 Nov;2(11):1471-1479. doi: 10.1038/s41564-017-0014-5. Epub 2017 Sep 4.
3
Genome-wide dissection of the quorum sensing signalling pathway in Trypanosoma brucei.对布鲁氏锥虫群体感应信号通路的全基因组剖析。
Nature. 2014 Jan 30;505(7485):681-685. doi: 10.1038/nature12864. Epub 2013 Dec 15.
4
A short bifunctional element operates to positively or negatively regulate ESAG9 expression in different developmental forms of Trypanosoma brucei.一个短的双功能元件在不同发育形式的布氏锥虫中正向或负向调控 ESAG9 表达。
J Cell Sci. 2013 May 15;126(Pt 10):2294-304. doi: 10.1242/jcs.126011. Epub 2013 Mar 22.
5
Identification of different trypanosome species in the mid-guts of tsetse flies of the Malanga (Kimpese) sleeping sickness focus of the Democratic Republic of Congo.在刚果民主共和国的 Malanga（金本巴）昏睡病焦点的采采蝇中肠内不同锥虫种的鉴定。
Parasit Vectors. 2012 Sep 19;5:201. doi: 10.1186/1756-3305-5-201.
6
A conserved trypanosomatid differentiation regulator controls substrate attachment and morphological development in Trypanosoma congolense.一个保守的锥虫分化调节因子控制着冈比亚锥虫中底物附着和形态发育。
PLoS Pathog. 2024 Feb 26;20(2):e1011889. doi: 10.1371/journal.ppat.1011889. eCollection 2024 Feb.
7
RNA-Seq analysis validates the use of culture-derived Trypanosoma brucei and provides new markers for mammalian and insect life-cycle stages.RNA-Seq 分析验证了培养的布氏锥虫的使用，并为哺乳动物和昆虫生活史阶段提供了新的标记物。
BMC Genomics. 2018 Apr 2;19(1):227. doi: 10.1186/s12864-018-4600-6.
8
Regulation of Trypanosoma brucei Total and Polysomal mRNA during Development within Its Mammalian Host.布氏锥虫在其哺乳动物宿主体内发育过程中总mRNA和多聚核糖体mRNA的调控
PLoS One. 2013 Jun 26;8(6):e67069. doi: 10.1371/journal.pone.0067069. Print 2013.
9
Positional Dynamics and Glycosomal Recruitment of Developmental Regulators during Trypanosome Differentiation.动粒定位和糖体募集在锥虫分化过程中的发育调控
mBio. 2019 Jul 9;10(4):e00875-19. doi: 10.1128/mBio.00875-19.
10
Mitochondrial DNA is critical for longevity and metabolism of transmission stage Trypanosoma brucei.线粒体 DNA 对于传播阶段布氏锥虫的寿命和代谢至关重要。
PLoS Pathog. 2018 Jul 18;14(7):e1007195. doi: 10.1371/journal.ppat.1007195. eCollection 2018 Jul.

引用本文的文献

1
Life stage-specific poly(A) site selection regulated by DRBD18.DRBD18 调控的生命阶段特异性 poly(A) 位点选择
Proc Natl Acad Sci U S A. 2024 Jul 16;121(29):e2403188121. doi: 10.1073/pnas.2403188121. Epub 2024 Jul 11.
2
Depolymerization of SUMO chains induces slender to stumpy differentiation in T. brucei bloodstream parasites.SUMO 链的解聚诱导 T. brucei 血流寄生虫从细长型向粗短型分化。
PLoS Pathog. 2024 Apr 18;20(4):e1012166. doi: 10.1371/journal.ppat.1012166. eCollection 2024 Apr.
3
A conserved trypanosomatid differentiation regulator controls substrate attachment and morphological development in Trypanosoma congolense.

本文引用的文献

1
Quantitative Proteomics Uncovers Novel Factors Involved in Developmental Differentiation of Trypanosoma brucei.定量蛋白质组学揭示了布氏锥虫发育分化过程中涉及的新因子。
PLoS Pathog. 2016 Feb 24;12(2):e1005439. doi: 10.1371/journal.ppat.1005439. eCollection 2016 Feb.
2
Species-Specific Adaptations of Trypanosome Morphology and Motility to the Mammalian Host.锥虫形态和运动对哺乳动物宿主的物种特异性适应
PLoS Pathog. 2016 Feb 12;12(2):e1005448. doi: 10.1371/journal.ppat.1005448. eCollection 2016 Feb.
3
Gene expression regulatory networks in Trypanosoma brucei: insights into the role of the mRNA-binding proteome.
一个保守的锥虫分化调节因子控制着冈比亚锥虫中底物附着和形态发育。
PLoS Pathog. 2024 Feb 26;20(2):e1011889. doi: 10.1371/journal.ppat.1011889. eCollection 2024 Feb.
4
The Occurrence of Malignancy in by Rapid Passage in Mice.小鼠快速传代过程中恶性肿瘤的发生情况 。 你提供的原文似乎不太完整，“by Rapid Passage in Mice”前面应该还有相关内容。
Front Microbiol. 2022 Jan 11;12:806626. doi: 10.3389/fmicb.2021.806626. eCollection 2021.
5
Establishment of quantitative RNAi-based forward genetics in Entamoeba histolytica and identification of genes required for growth.建立基于 RNAi 的定量正向遗传学在溶组织内阿米巴和鉴定生长所必需的基因。
PLoS Pathog. 2021 Nov 29;17(11):e1010088. doi: 10.1371/journal.ppat.1010088. eCollection 2021 Nov.
6
Selective nuclear export of mRNAs is promoted by DRBD18 in Trypanosoma brucei.mRNA 的选择性核输出是由布氏锥虫中的 DRBD18 促进的。
Mol Microbiol. 2021 Sep;116(3):827-840. doi: 10.1111/mmi.14773. Epub 2021 Jul 4.
7
Right place, right time: Environmental sensing and signal transduction directs cellular differentiation and motility in Trypanosoma brucei.恰到好处的时机：环境感应和信号转导指导布氏锥虫细胞的分化和运动。
Mol Microbiol. 2021 May;115(5):930-941. doi: 10.1111/mmi.14682.
8
A Trypanosoma brucei ORFeome-Based Gain-of-Function Library Identifies Genes That Promote Survival during Melarsoprol Treatment.布氏锥虫 ORFeome 为基础的功能获得文库鉴定出在美拉胂醇治疗期间促进存活的基因。
mSphere. 2020 Oct 7;5(5):e00769-20. doi: 10.1128/mSphere.00769-20.
9
Identification of clinically approved small molecules that inhibit growth and affect transcript levels of developmentally regulated genes in the African trypanosome.鉴定出能抑制非洲锥虫生长并影响其发育调控基因转录水平的临床批准小分子药物。
PLoS Negl Trop Dis. 2020 Mar 13;14(3):e0007790. doi: 10.1371/journal.pntd.0007790. eCollection 2020 Mar.
10
Positional Dynamics and Glycosomal Recruitment of Developmental Regulators during Trypanosome Differentiation.动粒定位和糖体募集在锥虫分化过程中的发育调控
mBio. 2019 Jul 9;10(4):e00875-19. doi: 10.1128/mBio.00875-19.
布氏锥虫中的基因表达调控网络：对mRNA结合蛋白质组作用的见解
Mol Microbiol. 2016 May;100(3):457-71. doi: 10.1111/mmi.13328. Epub 2016 Mar 10.
4
Molecular control of irreversible bistability during trypanosome developmental commitment.锥虫发育定向过程中不可逆双稳态的分子调控
J Cell Biol. 2015 Oct 26;211(2):455-68. doi: 10.1083/jcb.201506114. Epub 2015 Oct 19.
5
Novel insights into RNP granules by employing the trypanosome's microtubule skeleton as a molecular sieve.通过将锥虫的微管骨架用作分子筛，对核糖核蛋白颗粒有了新的认识。
Nucleic Acids Res. 2015 Sep 18;43(16):8013-32. doi: 10.1093/nar/gkv731. Epub 2015 Jul 17.
6
The within-host dynamics of African trypanosome infections.非洲锥虫感染在宿主体内的动态变化。
Philos Trans R Soc Lond B Biol Sci. 2015 Aug 19;370(1675). doi: 10.1098/rstb.2014.0288.
7
NMD3 regulates both mRNA and rRNA nuclear export in African trypanosomes via an XPOI-linked pathway.NMD3通过一种与XPO1相关的途径调节非洲锥虫中mRNA和rRNA的核输出。
Nucleic Acids Res. 2015 May 19;43(9):4491-504. doi: 10.1093/nar/gkv330. Epub 2015 Apr 14.
8
Assembling the components of the quorum sensing pathway in African trypanosomes.组装非洲锥虫群体感应途径的组件。
Mol Microbiol. 2015 Apr;96(2):220-32. doi: 10.1111/mmi.12949. Epub 2015 Mar 4.
9
Genome-scale RNAi screens for high-throughput phenotyping in bloodstream-form African trypanosomes.全基因组 RNAi 筛选用于高通量表型分析在血液循环期非洲锥虫。
Nat Protoc. 2015 Jan;10(1):106-33. doi: 10.1038/nprot.2015.005. Epub 2014 Dec 11.
10
A genome-wide tethering screen reveals novel potential post-transcriptional regulators in Trypanosoma brucei.全基因组拴系筛选揭示了布氏锥虫中新型潜在转录后调控因子。
PLoS Pathog. 2014 Jun 12;10(6):e1004178. doi: 10.1371/journal.ppat.1004178. eCollection 2014 Jun.