Lim L P, Sharp P A
Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Mol Cell Biol. 1998 Jul;18(7):3900-6. doi: 10.1128/MCB.18.7.3900.
The fibronectin EIIIB exon is alternatively spliced in a cell-type-specific manner, and TGCATG repeats in the intron downstream of EIIIB have been implicated in this regulation. Analysis of the intron sequence from several vertebrates shows that the pattern of repeats in the 3' half of the intron is evolutionarily conserved. Point mutations in certain highly conserved repeats greatly reduce EIIIB inclusion, suggesting that a multicomponent complex may recognize the repeats. Expression of the SR protein SRp40, SRp20, or ASF/SF2 stimulates EIIIB inclusion. Studies of the interplay between mutations in the repeats and SRp40-stimulated inclusion suggest that the repeats are recognized in many, if not all, cell types, and that EIIIB inclusion may be regulated by quantitative changes in multiple factors.
纤连蛋白EIIIB外显子以细胞类型特异性方式进行可变剪接,并且EIIIB下游内含子中的TGCATG重复序列与这种调控有关。对几种脊椎动物内含子序列的分析表明,内含子3'端一半的重复模式在进化上是保守的。某些高度保守重复序列中的点突变极大地减少了EIIIB的包含,这表明一个多组分复合物可能识别这些重复序列。SR蛋白SRp40、SRp20或ASF/SF2的表达刺激EIIIB的包含。对重复序列突变与SRp40刺激的包含之间相互作用的研究表明,这些重复序列在许多(如果不是所有)细胞类型中都能被识别,并且EIIIB的包含可能受多种因素定量变化的调控。