Schaal T D, Maniatis T
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Mol Cell Biol. 1999 Jan;19(1):261-73. doi: 10.1128/MCB.19.1.261.
We have identified multiple distinct splicing enhancer elements within protein-coding sequences of the constitutively spliced human beta-globin pre-mRNA. Each of these highly conserved sequences is sufficient to activate the splicing of a heterologous enhancer-dependent pre-mRNA. One of these enhancers is activated by and binds to the SR protein SC35, whereas at least two others are activated by the SR protein SF2/ASF. A single base mutation within another enhancer element inactivates the enhancer but does not change the encoded amino acid. Thus, overlapping protein coding and RNA recognition elements may be coselected during evolution. These studies provide the first direct evidence that SR protein-specific splicing enhancers are located within the coding regions of constitutively spliced pre-mRNAs. We propose that these enhancers function as multisite splicing enhancers to specify 3' splice-site selection.
我们已在组成型剪接的人β-珠蛋白前体mRNA的蛋白质编码序列中鉴定出多个不同的剪接增强子元件。这些高度保守的序列中的每一个都足以激活异源增强子依赖性前体mRNA的剪接。其中一个增强子被SR蛋白SC35激活并与之结合，而至少另外两个增强子被SR蛋白SF2/ASF激活。另一个增强子元件内的单个碱基突变会使增强子失活，但不会改变编码的氨基酸。因此，重叠的蛋白质编码和RNA识别元件可能在进化过程中被共同选择。这些研究提供了首个直接证据，表明SR蛋白特异性剪接增强子位于组成型剪接的前体mRNA的编码区域内。我们提出，这些增强子作为多位点剪接增强子发挥作用，以指定3'剪接位点的选择。
