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Proc Natl Acad Sci U S A
2005 Apr 05;10214:5002-7. doi: 10.1073/pnas.0500543102.
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Serine/arginine-rich protein-dependent suppression of exon skipping by exonic splicing enhancers.
Ibrahim EC
,
Schaal TD
,
Hertel KJ
,
Reed R
,
Maniatis T
.
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The 5' and 3' splice sites within an intron can, in principle, be joined to those within any other intron during pre-mRNA splicing. However, exons are joined in a strict 5' to 3' linear order in constitutively spliced pre-mRNAs. Thus, specific mechanisms must exist to prevent the random joining of exons. Here we report that insertion of exon sequences into an intron can inhibit splicing to the downstream 3' splice site and that this inhibition is independent of intron size. The exon sequences required for splicing inhibition were found to be exonic enhancer elements, and their inhibitory activity requires the binding of serine/arginine-rich splicing factors. We conclude that exonic enhancers can act as barriers to prevent exon skipping and thereby may play a key role in ensuring the correct 5' to 3' linear order of exons in spliced mRNA.
Berget,
Exon recognition in vertebrate splicing.
1995, Pubmed
Berget,
Exon recognition in vertebrate splicing.
1995,
Pubmed
Black,
Mechanisms of alternative pre-messenger RNA splicing.
2003,
Pubmed
Black,
Alternative pre-mRNA splicing and neuronal function.
2003,
Pubmed
Black,
A simple answer for a splicing conundrum.
2005,
Pubmed
Blencowe,
Exonic splicing enhancers: mechanism of action, diversity and role in human genetic diseases.
2000,
Pubmed
Boukis,
Ser/Arg-rich protein-mediated communication between U1 and U2 small nuclear ribonucleoprotein particles.
2004,
Pubmed
Cartegni,
Listening to silence and understanding nonsense: exonic mutations that affect splicing.
2002,
Pubmed
Cavaloc,
The splicing factors 9G8 and SRp20 transactivate splicing through different and specific enhancers.
1999,
Pubmed
Dauksaite,
Human splicing factor ASF/SF2 encodes for a repressor domain required for its inhibitory activity on pre-mRNA splicing.
2002,
Pubmed
Expert-Bezançon,
hnRNP A1 and the SR proteins ASF/SF2 and SC35 have antagonistic functions in splicing of beta-tropomyosin exon 6B.
2004,
Pubmed
Fu,
The 35-kDa mammalian splicing factor SC35 mediates specific interactions between U1 and U2 small nuclear ribonucleoprotein particles at the 3' splice site.
1992,
Pubmed
Gallego,
The SR splicing factors ASF/SF2 and SC35 have antagonistic effects on intronic enhancer-dependent splicing of the beta-tropomyosin alternative exon 6A.
1997,
Pubmed
Graveley,
Sorting out the complexity of SR protein functions.
2000,
Pubmed
Hastings,
Pre-mRNA splicing in the new millennium.
2001,
Pubmed
Hastings,
A purine-rich intronic element enhances alternative splicing of thyroid hormone receptor mRNA.
2001,
Pubmed
Hertel,
Serine-arginine (SR)-rich splicing factors have an exon-independent function in pre-mRNA splicing.
1999,
Pubmed
Kanopka,
Inhibition by SR proteins of splicing of a regulated adenovirus pre-mRNA.
1996,
Pubmed
Kohtz,
Protein-protein interactions and 5'-splice-site recognition in mammalian mRNA precursors.
1994,
Pubmed
Kornblihtt,
Multiple links between transcription and splicing.
2004,
Pubmed
Krainer,
Normal and mutant human beta-globin pre-mRNAs are faithfully and efficiently spliced in vitro.
1984,
Pubmed
Liu,
Identification of functional exonic splicing enhancer motifs recognized by individual SR proteins.
1998,
Pubmed
Lou,
Regulation of alternative polyadenylation by U1 snRNPs and SRp20.
1998,
Pubmed
Luo,
Splicing is required for rapid and efficient mRNA export in metazoans.
1999,
Pubmed
,
Xenbase
Lynch,
Synergistic interactions between two distinct elements of a regulated splicing enhancer.
1995,
Pubmed
Pagani,
Splicing factors induce cystic fibrosis transmembrane regulator exon 9 skipping through a nonevolutionary conserved intronic element.
2000,
Pubmed
Reed,
Intron sequences involved in lariat formation during pre-mRNA splicing.
1985,
Pubmed
Reed,
A role for exon sequences and splice-site proximity in splice-site selection.
1986,
Pubmed
Reed,
The role of the mammalian branchpoint sequence in pre-mRNA splicing.
1988,
Pubmed
Reed,
Mechanisms of fidelity in pre-mRNA splicing.
2000,
Pubmed
Schaal,
Multiple distinct splicing enhancers in the protein-coding sequences of a constitutively spliced pre-mRNA.
1999,
Pubmed
Schaal,
Selection and characterization of pre-mRNA splicing enhancers: identification of novel SR protein-specific enhancer sequences.
1999,
Pubmed
Shen,
A pathway of sequential arginine-serine-rich domain-splicing signal interactions during mammalian spliceosome assembly.
2004,
Pubmed
Shen,
Arginine-serine-rich domains bound at splicing enhancers contact the branchpoint to promote prespliceosome assembly.
2004,
Pubmed
Simard,
SRp30c is a repressor of 3' splice site utilization.
2002,
Pubmed
Tian,
A splicing enhancer complex controls alternative splicing of doublesex pre-mRNA.
1993,
Pubmed
Treisman,
Structural and functional defects in beta-thalassemia.
1983,
Pubmed
Wu,
Specific interactions between proteins implicated in splice site selection and regulated alternative splicing.
1993,
Pubmed
Zahler,
Purification of SR protein splicing factors.
1999,
Pubmed
Zhu,
Exon identity established through differential antagonism between exonic splicing silencer-bound hnRNP A1 and enhancer-bound SR proteins.
2001,
Pubmed