title: Sequence features involved in the mechanism of 3' splice junction wobbling.
abstract: BACKGROUND
  Alternative splicing is an important mechanism mediating the diversified functions of genes in multicellular organisms, and such event occurs in around 40-60% of human genes. Recently, a new splice-junction wobbling mechanism was proposed that subtle modifications exist in mRNA maturation by alternatively choosing at 5'- GTNGT and 3'- NAGNAG, which created single amino acid insertion and deletion isoforms.
  
  
  RESULTS
  By browsing the Alternative Splicing Database information, we observed that most 3' alternative splice site choices occur within six nucleotides of the dominant splice site and the incidence significantly decreases further away from the dominant acceptor site. Although a lower frequency of alternative splicing occurs within the intronic region (alternative splicing at the proximal AG) than in the exonic region (alternative splicing at the distal AG), alternative AG sites located within the intronic region show stronger potential as the acceptor. These observations revealed that the choice of 3' splice sites during 3' splicing junction wobbling could depend on the distance between the duplicated AG and the branch point site (BPS). Further mutagenesis experiments demonstrated that the distance of AG-to-AG and BPS-to-AG can greatly influence 3' splice site selection. Knocking down a known alternative splicing regulator, hSlu7, failed to affect wobble splicing choices.
  
  
  CONCLUSIONS
  Our results implied that nucleotide distance between proximal and distal AG sites has an important regulatory function. In this study, we showed that occurrence of 3' wobble splicing occurs in a distance-dependent manner and that most of this wobble splicing is probably caused by steric hindrance from a factor bound at the neighboring tandem motif sequence.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. wenlin@ibms.sinica.edu.tw
authors.forename: Kuo-Wang
authors.initials: KW
authors.lastname: Tsai
authors.forename: Wen-Ching
authors.initials: WC
authors.lastname: Chan
authors.forename: Chun-Nan
authors.initials: CN
authors.lastname: Hsu
authors.forename: Wen-Chang
authors.initials: WC
authors.lastname: Lin
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D030561:Databases, Nucleic Acid; D006801:Humans; D022821:RNA Splice Sites
chemical_list: D022821:RNA Splice Sites
references.citation: Cancer Res. 2007 Mar 15;67(6):2552-8
references.pmid: 17363573
references.citation: Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):11960-4
references.pmid: 8618823
references.citation: Curr Opin Genet Dev. 1996 Apr;6(2):215-20
references.pmid: 8722179
references.citation: PLoS Genet. 2006 Apr;2(4):e45
references.pmid: 16683028
references.citation: Genome Res. 2003 Jun;13(6B):1290-300
references.pmid: 12819126
references.citation: BMC Genomics. 2008 Apr 10;9:159
references.pmid: 18402682
references.citation: Nucleic Acids Res. 2004 Jan 1;32(Database issue):D64-9
references.pmid: 14681360
references.citation: Nature. 1989 Nov 16;342(6247):243-7
references.pmid: 2812024
references.citation: Nat Rev Mol Cell Biol. 2004 Feb;5(2):89-99
references.pmid: 15040442
references.citation: Cell. 1998 Feb 6;92(3):315-26
references.pmid: 9476892
references.citation: Curr Opin Cell Biol. 2000 Jun;12(3):340-5
references.pmid: 10801464
references.citation: Trends Biochem Sci. 2005 Sep;30(9):515-21
references.pmid: 16023350
references.citation: Biochem Biophys Res Commun. 2006 Mar 31;342(1):197-205
references.pmid: 16472775
references.citation: Exp Cell Res. 2008 Oct 15;314(17):3130-41
references.pmid: 18775696
references.citation: Am J Hum Genet. 1999 Apr;64(4):1024-35
references.pmid: 10090887
references.citation: Curr Opin Struct Biol. 2004 Jun;14(3):273-82
references.pmid: 15193306
references.citation: Genome Biol. 2006;7(7):R65
references.pmid: 16869967
references.citation: Nucleic Acids Res. 2009 Jun;37(11):3569-79
references.pmid: 19359358
references.citation: RNA. 2008 Apr;14(4):616-29
references.pmid: 18268022
references.citation: Mol Cell Biol. 2007 Aug;27(16):5835-48
references.pmid: 17562859
references.citation: Annu Rev Biochem. 2003;72:291-336
references.pmid: 12626338
references.citation: Genomics. 2006 Dec;88(6):855-864
references.pmid: 16920330
references.citation: Mol Cell Biol. 1996 Dec;16(12):6677-86
references.pmid: 8943322
references.citation: J Biol Chem. 1994 Mar 18;269(11):8510-6
references.pmid: 7510688
references.citation: Nucleic Acids Res. 2006 Jan 03;34(1):23-31
references.pmid: 16394021
references.citation: Am J Hum Genet. 2006 Feb;78(2):291-302
references.pmid: 16400609
references.citation: Eukaryot Cell. 2003 Oct;2(5):830-40
references.pmid: 14555465
references.citation: Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):593-8
references.pmid: 10639124
references.citation: Mol Cell Biol. 2001 Mar;21(5):1509-14
references.pmid: 11238888
references.citation: Mol Cell Biol. 1993 Aug;13(8):4939-52
references.pmid: 8336728
references.citation: Trends Genet. 2004 May;20(5):232-6
references.pmid: 15109776
references.citation: J Biol Chem. 2006 Nov 10;281(45):34677-86
references.pmid: 16973615
references.citation: RNA. 2006 Dec;12(12):2047-56
references.pmid: 17053087
references.citation: Nature. 1999 Nov 11;402(6758):207-10
references.pmid: 10647016
references.citation: Biochem Biophys Res Commun. 2007 Jun 29;358(2):590-5
references.pmid: 17498651
references.citation: Nat Genet. 2004 Dec;36(12):1255-7
references.pmid: 15516930
references.citation: J Clin Endocrinol Metab. 1999 Nov;84(11):4283-6
references.pmid: 10566686
references.citation: J Hum Genet. 2005;50(8):382-394
references.pmid: 16091834
references.citation: Pac Symp Biocomput. 2004;:66-77
references.pmid: 14992493
references.citation: Gene. 1999 Apr 1;230(1):55-60
references.pmid: 10196474