Goren Amir, Ram Oren, Amit Maayan, Keren Hadas, Lev-Maor Galit, Vig Ida, Pupko Tal, Ast Gil
Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Mol Cell. 2006 Jun 23;22(6):769-781. doi: 10.1016/j.molcel.2006.05.008.
Exonic splicing regulatory sequences (ESRs) are cis-acting factor binding sites that regulate constitutive and alternative splicing. A computational method based on the conservation level of wobble positions and the overabundance of sequence motifs between 46,103 human and mouse orthologous exons was developed, identifying 285 putative ESRs. Alternatively spliced exons that are either short in length or contain weak splice sites show the highest conservation level of those ESRs, especially toward the edges of exons. ESRs that are abundant in those subgroups show a different distribution between constitutively and alternatively spliced exons. Representatives of these ESRs and two SR protein binding sites were shown, experimentally, to display variable regulatory effects on alternative splicing, depending on their relative locations in the exon. This finding signifies the delicate positional effect of ESRs on alternative splicing regulation.
外显子剪接调控序列（ESRs）是调节组成型剪接和可变剪接的顺式作用因子结合位点。基于46103个人类和小鼠直系同源外显子之间摆动位置的保守水平和序列基序的丰度，开发了一种计算方法，鉴定出285个推定的ESRs。长度较短或包含弱剪接位点的可变剪接外显子显示出这些ESRs的最高保守水平，尤其是在外显子边缘。在这些亚组中丰富的ESRs在组成型剪接和可变剪接外显子之间表现出不同的分布。实验表明，这些ESRs的代表和两个SR蛋白结合位点根据它们在外显子中的相对位置，对可变剪接显示出不同的调控作用。这一发现表明ESRs在可变剪接调控中具有微妙的位置效应。
