Hui Jingyi, Stangl Karl, Lane William S, Bindereif Albrecht
Institut für Biochemie, Justus-Liebig-Universität Giessen, Heinrich-Buff-Ring 58, D-35392 Giessen, Germany.
Nat Struct Biol. 2003 Jan;10(1):33-7. doi: 10.1038/nsb875.
In the human genome, dinucleotide repeats are common sequence elements of unknown functional significance. Here we demonstrate that CA repeats in intron 13 of the human endothelial nitric oxide synthase (eNOS) gene function as an unusual intronic splicing enhancer, whose activity depends on the CA repeat number. We identify the 65 kDa heterogenous nuclear ribonucleoprotein (hnRNP) L as the major factor that binds specifically and in a length-dependent manner to the CA-repeat enhancer. In addition, we show that hnRNP L functions as a specific activator of eNOS splicing, providing the first evidence for a role of hnRNP L in the regulation of mRNA splicing. We hypothesize that hnRNP L may be involved in the regulation of many other genes containing CA repeats or A/C-rich enhancers.
在人类基因组中，二核苷酸重复序列是功能意义未知的常见序列元件。在此我们证明，人类内皮型一氧化氮合酶（eNOS）基因第13内含子中的CA重复序列作为一种不同寻常的内含子剪接增强子发挥作用，其活性取决于CA重复序列的数目。我们鉴定出65 kDa异质性核核糖核蛋白（hnRNP）L是与CA重复序列增强子特异性且以长度依赖方式结合的主要因子。此外，我们表明hnRNP L作为eNOS剪接的特异性激活因子发挥作用，为hnRNP L在mRNA剪接调控中的作用提供了首个证据。我们推测，hnRNP L可能参与调控许多其他含有CA重复序列或富含A/C增强子的基因。
