An exonic splicing enhancer offsets the atypical GU-rich 3' splice site of human apolipoprotein A-II exon 3

The Journal of Biological Chemistry
Pablo Arrisi-MercadoFrancisco E Baralle

Abstract

Human apolipoprotein A-II (apoA-II) intron 2/exon 3 junction shows a peculiar tract of alternating pyrimidines and purines (GU tract) that makes the acceptor site deviate significantly from the consensus. However, apoA-II exon 3 is constitutively included in mRNA. We have studied this unusual exon definition by creating a construct with the genomic fragment encompassing the whole gene from apoA-II and its regulatory regions. Transient transfections in Hep3B cells have shown that deletion or replacement of the GU repeats at the 3' splice site resulted in a decrease of apoA-II exon 3 inclusion, indicating a possible role of the GU tract in splicing. However, a 3' splice site composed of the GU tract in heterologous context, such as the extra domain A of human fibronectin or cystic fibrosis transmembrane conductance regulator exon 9, resulted in total skipping of the exons. Next, we identified the exonic cis-acting elements that may affect the splicing efficiency of apoA-II exon 3 and found that the region spanning from nucleotide 87 to 113 of human apoA-II exon 3 is essential for its inclusion in the mRNA. Overlapping deletions and point mutations (between nucleotides 91 and 102) precisely defined an exonic splicing enhancer (ESE...Continue Reading

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Citations

Oct 29, 2005·Nucleic Acids Research·Pablo Arrisi MercadoFrancisco E Baralle
Aug 12, 2015·Proceedings of the National Academy of Sciences of the United States of America·Jian ZhangJames L Manley
Oct 18, 2011·The EMBO Journal·Gerrit M DaubnerFrédéric H-T Allain
Aug 22, 2009·Muscle & Nerve·Stephen J KolbDaniel R Schoenberg
Oct 30, 2008·Journal of Cell Science·Youhna M AyalaFrancisco E Baralle

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