期刊文献+

A large-scale functional approach to uncover human genes and pathways in Drosophila 被引量:5

A large-scale functional approach to uncover human genes and pathways in Drosophila
下载PDF
导出
摘要 我们表明为他们导致 overexpression 显型的能力由 assaying 在果蝇为人的基因功能执行一幅系统的屏幕的可行性。相应于 236 人的基因的超过 1 500 根转基因的苍蝇线被建立了。总共, 51 根线能够得到建议人的基因是功能的显型。当我们发现类似的变异的显型也被主导的否定异种引起了,这些 heterologous 基因是机能上地相关的人的 ribosomal 蛋白质 L8 基因或由果蝇 RPL8 的 RNAi downregulation 的形式。显著地,果蝇 RPL8 异种能被野类型的人的 RPL8 救。我们也提供果蝇 RPL8 是表明小径的胰岛素的一个新成员的基因证据。在摘要,许多人的基因的功能出现到高度被保存,并且在果蝇识别他们的能力在 vivo 为人的抄本的大规模分析代表一个强大的基因工具。 We demonstrate the feasibility of performing a systematic screen for human gene functions in Drosophila by assaying for their ability to induce overexpression phenotypes. Over 1 500 transgenic fly lines corresponding to 236 human genes have been established. In all, 51 lines are capable of eliciting a phenotype suggesting that the human genes are functional. These heterologous genes are functionally relevant as we have found a similar mutant phenotype caused either by a dominant negative mutant form of the human ribosomal protein L8 gene or by RNAi downregulation of the Drosophila RPL8. Significantly, the Drosophila RPL8 mutant can be rescued by wild-type human RPL8. We also provide genetic evidence that Drosophila RPL8 is a new member of the insulin signaling pathway. In summary, the functions of many human genes appear to be highly conserved, and the ability to identify them in Drosophila represents a powerful genetic tool for large-scale analysis of human transcripts in vivo.
出处 《Cell Research》 SCIE CAS CSCD 2008年第11期1114-1127,共14页 细胞研究(英文版)
基金 We are grateful to Xizhi Ma, Junnian Zhou, Tianhong Xu, Xu Liu, Xu Ding, Yang Liu, Ying Peng, Congwu Chi, Yiying Shang, Mingyao Ying, Sheng Ding, Lei Sun, Lei Tian, Huanhu Zhu, Hua Huang, Hongmei Li, and Xiaomo Wu for cDNA constructs and partial transgenic work, and Lihui Zhou (East China University of Science and Technology, China) for scanning electron microscopy. We thank Duc Nguyen (Yale University, USA) for critical reading and editing of this manuscript. This work is supported by grants from the National Natural Science Foundation of China (Grant Nos. 30030080, 39970408 and 30470840), National Basic Research Program of China (973) (Grant No. 2006CB806700).
关键词 遗传基因 显性 GAL4/UAS 可行性 细胞 Drosophila, human gene, GAL4/UAS, genetic screen, RPL8, insulin signaling
  • 相关文献

参考文献44

  • 1Benson DA, Karsch-Mizrachi I, Lipman D J, Ostell J, Wheeler DL. GenBank. Nucleic Acids Res 2006; 34:D16-D20.
  • 2Venter JC, Adams MD, Myers EW, et al. The sequence of the human genome. Science 2001; 291:1304-1351.
  • 3Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the human genome. Nature 2001; 409:860-921.
  • 4Collins FS, Green ED, Guttmacher AE, Guyer MS. A vision for the future of genomics research. Nature 2003; 422:835- 847.
  • 5Adams MD, Celniker SE, Holt RA, et al. The genome sequence of Drosophila melanogaster. Science 2000; 287:2185- 2195.
  • 6Phelps CB, Brand AH. Ectopic gene expression in Drosophila using GAL4 system. Methods 1998; 14: 367-379.
  • 7Rφrth P. A modular misexpression screen in Drosophila detecting tissue-specific phenotypes. Proc Natl Acad Sci USA 1996; 93:12418-12422.
  • 8Brand AH, Perrimon N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 1993; 118:401-415.
  • 9Crosby MA, Goodman JL, Strelets VB, Zhang P, Gelbart WM, FlyBase Consortium. FlyBase: genomes by the dozen. Nucleic Acids Res 2007; 35:D486-D491.
  • 10Freeman M. Reiterative use of the EGF receptor triggers differentiation of all cell types in the Drosophila eye. Cell 1996; 87:651-660.

同被引文献39

  • 1W. Yean Chooi,Steve M. James,Daniel K. Burns.Decrease in ribosomal proteins 1, 2/3, L4, and L7 in Drosophila melanogaster in the absence of X rDNA[J]. MGG Molecular & General Genetics . 1982 (3)
  • 2Enerly E,Larsson J,Lambertsson A.Silencing the Drosophila ribo- somal protein L14 gene using targeted RNA interference causes dis- tinct somatic anomalies. Gene . 2003
  • 3Ni J Q,Liu L P,Hess Det al.Drosophila ribosomal proteins are as- sociated with linker histone H1 and suppress gene transcription. Genes and Development . 2006
  • 4Lohrum M A,Ludwig R L,Kubbutat M Het al.Regulation of HDM2 activity by the ribosomal protein L11. Cancer Cell . 2003
  • 5Soulet F,Al Saati T,Roga Set al.Fibroblast growth factor-2 inter- acts with free ribosomal protein S19. Biochemical and Biophysical Research Communications . 2001
  • 6Grether M E,Abrams J M,Agapite Jet al.The head involution de- fective gene of Drosophila melanogaster functions in programmed cell death. Genes and Development . 1995
  • 7White K,Tahaoglu E,Steller H.Cell killing by the Drosophila gene reaper. Science . 1996
  • 8Zhou L,Schnitzler A,Agapite Jet al.Cooperative functions of the reaper and head involution defective genes in the programmed cell death of Drosophila central nervous system midline cells. Proceedings of the National Academy of Sciences of the United States of America . 1997
  • 9Pollok S,Bauerschmidt C,Sanger Jet al.Human Cdc45 is a prolif- eration-associated antigen. Febs J . 2007
  • 10Krause K,Wasner M,Reinhard Wet al.The tumour suppressor pro- tein p53 can repress transcription of cyclin B. Nucleic Acids Research . 2000

引证文献5

二级引证文献4

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部