Wagner Eric J, Garcia-Blanco Mariano A
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Mol Cell. 2002 Oct;10(4):943-9. doi: 10.1016/s1097-2765(02)00645-7.
Mutually exclusive use of exons IIIb or IIIc in FGF-R2 transcripts requires the silencing of exon IIIb. This repression is mediated by silencer elements upstream and downstream of the exon. Both silencers bind the polypyrimidine tract binding protein (PTB) and PTB binding sites within these elements are required for efficient silencing of exon IIIb. Recruitment of MS2-PTB fusion proteins upstream or downstream of exon IIIb causes repression of this exon. Depletion of endogenous PTB using RNAi increases exon IIIb inclusion in transcripts derived from minigenes and from the endogenous FGF-R2 gene. These data demonstrate that PTB is a negative regulator of exon definition in vivo.
FGF-R2转录本中外显子IIIb或IIIc的互斥使用需要外显子IIIb的沉默。这种抑制作用由该外显子上下游的沉默子元件介导。两个沉默子均与多嘧啶序列结合蛋白（PTB）结合，并且这些元件内的PTB结合位点对于外显子IIIb的有效沉默是必需的。在外显子IIIb上游或下游募集MS2-PTB融合蛋白会导致该外显子的抑制。使用RNAi耗尽内源性PTB会增加来自小基因和内源性FGF-R2基因的转录本中外显子IIIb的包含率。这些数据表明，PTB在体内是外显子界定的负调节因子。
