度减慢，或中间停顿，则有利于可变剪接外显子上 游的内含子的切除，一般该内含子3’剪接位点效应较弱。等RNA POLⅡ继续前进，剪接体只 能切除下游的内含子，使得可变外显子保留。如果RNA POLⅡ延伸速度快，或没有中间停 顿，则两个3’ 剪接位点之间竞争，下游的强3’ 剪接位点效应更强，导致了可变外显子的去 除。另外，延伸速率对RNA二级结构的作用，或RNA POLⅡ停止位点迟缓ESE，ESS转录的 作用，也影响可变剪接。 结束语： 发现新的可变剪接异构体， 确定每个异构体的独特功能和生物学意义， 并阐明其调节机
制，是功能基因组时代研究的一个重要领域。在这一领域研究中，除利用经典的分子生物学 技术外，还需建立新的高通量的技术，如生物芯片技术，RNAi 技术等，并要与生物信息学 技术紧密结合，同时需要细胞生物学、生物化学、临床与病理学、免疫学等多学科的协作， 才有可能对这一重要的生命现象有所了解。 参考文献 1 Ewing, B. and Green, P. (2000 Analysis of expressed sequence tags indicates 35,000 human genes. Nat. Genet. 25, 232–234 2. Adams, M.D. et al. The genome sequence of Drosophila melanogaster. Science 287, 2185–2195 (2000. 3. The C. elegans Sequencing Consortium. Genome sequence of the nematode C. 4 Pennisi, E. Human genome project: and the gene number is...? Science 288, 1146–1147 (2000. 5 Brenton R. Graveley Alternative splicing: increasing diversity in the proteomic world. TRENDS in Genetics Vol.17 No.2 February 2001 6. Barmak Modrek & Christopher Lee. A genomic view of alternative splicing nature genetics ? volume 30,13-19 ?January 2002 7. Javier F. Cá ceres and Alberto R. Kornblihtt Alternative splicing: multiple control mechanisms and involvement in human disease TRENDS in Genetics Vol.18 No.4,186-193 April 2002 8 Michelle L Hastings and Adrian R Krainer Pre-mRNA splicing in the new millennium. Current Opinion in Cell Biology 2001, 13:302–309 9 Douglas L. Black Protein Diversity from Alternative Splicing: A Challenge for Bioinformatics and Post-Genome Biology. Cell, Vol. 103, 367–370, October 27, 2000, 10 Aaron C. Goldstrohm, Arno L. Greenleaf, Mariano A. Garcia-Blanco . Co-transcriptional splicing of pre-messenger RNAs: considerations for the mechanism of alternative splicing. Gene 277 (2001 31–47 11
Malka Nissim-Rafinia and Batsheva Kerem TRENDS in Genetics Vol.18 No.3 March 2002
可变剪接与蛋白质组多样性及其调节机制解读
