Nucleic Acids Research Advance Access originally published online on March 1, 2007
Nucleic Acids Research 2007 35(6):1833-1841; doi:10.1093/nar/gkm026
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Nucleic Acids Research, 2007, Vol. 35, No. 6 1833-1841
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Alternative splicing and bioinformatic analysis of human U12-type introns
1Graduate Institute of Life Sciences, National Defense Medical Center, 2Institute of Biomedical Sciences, Academia Sinica, 3Institute of Microbiology and Immunology, College of Life Science, National Yang-Ming University and 4Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taiwan
*To whom correspondence should be addressed. Tel: 8862 2652 3052; Fax: 8862 2782 9142; Email: wtarn{at}ibms.sinica.edu.tw
Received September 29, 2006. Revised January 1, 2007. Accepted January 4, 2007.
U12-type introns exist, albeit rarely, in a variety of multicellular organisms. Splicing of U12 intron-containing precursor mRNAs takes place in the U12-type spliceosome that is distinct from the major U2-type spliceosome. Due to incompatibility of these two spliceosomes, alternative splicing involving a U12-type intron may give rise to a relatively complicated impact on gene expression. We studied alternative U12-type intron splicing in an attempt to gain more mechanistic insights. First, we characterized mutually exclusive exon selection of the human JNK2 gene, which involves an unusual intron possessing the U12-type 5' splice site and the U2-type 3' splice site. We demonstrated that the long and evolutionary conserved polypyrimidine tract of this hybrid intron provides important signals for inclusion of its downstream alternative exon. In addition, we examined the effects of single nucleotide polymorphisms in the human WDFY1 U12-type intron on pre-mRNA splicing. These results provide mechanistic implications on splice-site selection of U12-type intron splicing. We finally discuss the potential effects of splicing of a U12-type intron with genetic defects or within a set of genes encoding RNA processing factors on global gene expression.