Sequence features involved in the mechanism of 3' splice junction wobbling.
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.
Tsai
Kuo-Wang
KW
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. wenlin@ibms.sinica.edu.tw
Chan
Wen-Ching
WC
Hsu
Chun-Nan
CN
Lin
Wen-Chang
WC
D017398:Alternative Splicing; D001483:Base Sequence; D030561:Databases, Nucleic Acid; D006801:Humans; D022821:RNA Splice Sites
D022821:RNA Splice Sites
Cancer Res. 2007 Mar 15;67(6):2552-8
17363573
Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):11960-4
8618823
Curr Opin Genet Dev. 1996 Apr;6(2):215-20
8722179
PLoS Genet. 2006 Apr;2(4):e45
16683028
Genome Res. 2003 Jun;13(6B):1290-300
12819126
BMC Genomics. 2008 Apr 10;9:159
18402682
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D64-9
14681360
Nature. 1989 Nov 16;342(6247):243-7
2812024
Nat Rev Mol Cell Biol. 2004 Feb;5(2):89-99
15040442
Cell. 1998 Feb 6;92(3):315-26
9476892
Curr Opin Cell Biol. 2000 Jun;12(3):340-5
10801464
Trends Biochem Sci. 2005 Sep;30(9):515-21
16023350
Biochem Biophys Res Commun. 2006 Mar 31;342(1):197-205
16472775
Exp Cell Res. 2008 Oct 15;314(17):3130-41
18775696
Am J Hum Genet. 1999 Apr;64(4):1024-35
10090887
Curr Opin Struct Biol. 2004 Jun;14(3):273-82
15193306
Genome Biol. 2006;7(7):R65
16869967
Nucleic Acids Res. 2009 Jun;37(11):3569-79
19359358
RNA. 2008 Apr;14(4):616-29
18268022
Mol Cell Biol. 2007 Aug;27(16):5835-48
17562859
Annu Rev Biochem. 2003;72:291-336
12626338
Genomics. 2006 Dec;88(6):855-864
16920330
Mol Cell Biol. 1996 Dec;16(12):6677-86
8943322
J Biol Chem. 1994 Mar 18;269(11):8510-6
7510688
Nucleic Acids Res. 2006 Jan 03;34(1):23-31
16394021
Am J Hum Genet. 2006 Feb;78(2):291-302
16400609
Eukaryot Cell. 2003 Oct;2(5):830-40
14555465
Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):593-8
10639124
Mol Cell Biol. 2001 Mar;21(5):1509-14
11238888
Mol Cell Biol. 1993 Aug;13(8):4939-52
8336728
Trends Genet. 2004 May;20(5):232-6
15109776
J Biol Chem. 2006 Nov 10;281(45):34677-86
16973615
RNA. 2006 Dec;12(12):2047-56
17053087
Nature. 1999 Nov 11;402(6758):207-10
10647016
Biochem Biophys Res Commun. 2007 Jun 29;358(2):590-5
17498651
Nat Genet. 2004 Dec;36(12):1255-7
15516930
J Clin Endocrinol Metab. 1999 Nov;84(11):4283-6
10566686
J Hum Genet. 2005;50(8):382-394
16091834
Pac Symp Biocomput. 2004;:66-77
14992493
Gene. 1999 Apr 1;230(1):55-60
10196474