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Intronic CA‐repeat and CA‐rich elements: a new class of regulators of mammalian alternative splicing
Author(s) -
Hui Jingyi,
Hung LeeHsueh,
Heiner Monika,
Schreiner Silke,
Neumüller Norma,
Reither Gregor,
Haas Stefan A,
Bindereif Albrecht
Publication year - 2005
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600677
Subject(s) - minigene , biology , alternative splicing , rna splicing , enhancer , intron , genetics , sr protein , gene , human genome , regulatory sequence , exonic splicing enhancer , splicing factor , rna , exon , genome , regulation of gene expression , gene expression
We have recently identified an intronic polymorphic CA‐repeat region in the human endothelial nitric oxide synthase ( eNOS ) gene as an important determinant of the splicing efficiency, requiring specific binding of hnRNP L. Here, we analyzed the position requirements of this CA‐repeat element, which revealed its potential role in alternative splicing. In addition, we defined the RNA binding specificity of hnRNP L by SELEX: not only regular CA repeats are recognized with high affinity but also certain CA‐rich clusters. Therefore, we have systematically searched the human genome databases for CA‐repeat and CA‐rich elements associated with alternative 5′ splice sites (5′ss), followed by minigene transfection assays. Surprisingly, in several specific human genes that we tested, intronic CA RNA elements could function either as splicing enhancers or silencers, depending on their proximity to the alternative 5′ss. HnRNP L was detected specifically bound to these diverse CA elements. These data demonstrated that intronic CA sequences constitute novel and widespread regulatory elements of alternative splicing.