Abstract / Description of output
Abundance of pseudo splice sites in introns can potentially give rise to innumerable pseudoexons, outnumbering the real ones. Nonetheless, these are efficiently ignored by the splicing machinery, a process yet to be understood completely. Although numerous 5' splice site-like sequences functioning as splicing silencers have been found to be enriched in predicted human pseudoexons, the lack of active pseudoexons pose a fundamental challenge to how these U1snRNP-binding sites function in splicing inhibition. Here, we address this issue by focusing on a previously described pathological ATM pseudoexon whose inhibition is mediated by U1snRNP binding at intronic splicing processing element (ISPE), composed of a consensus donor splice site. Spliceosomal complex assembly demonstrates inefficient A complex formation when ISPE is intact, implying U1snRNP-mediated unproductive U2snRNP recruitment. Furthermore, interaction of SF2/ASF with its motif seems to be dependent on RNA structure and U1snRNP interaction. Our results suggest a complex combinatorial interplay of RNA structure and trans-acting factors in determining the splicing outcome and contribute to understanding the intronic splicing code for the ATM pseudoexon.
Original language | English |
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Pages (from-to) | 749-60 |
Number of pages | 12 |
Journal | EMBO Journal |
Volume | 29 |
Issue number | 4 |
DOIs | |
Publication status | Published - 17 Feb 2010 |
Keywords / Materials (for Non-textual outputs)
- Ataxia Telangiectasia/genetics
- Ataxia Telangiectasia Mutated Proteins
- Base Sequence
- Binding Sites/genetics
- Cell Cycle Proteins/genetics
- DNA Primers/genetics
- DNA-Binding Proteins/genetics
- Exons
- Heterogeneous Nuclear Ribonucleoprotein A1
- Heterogeneous-Nuclear Ribonucleoprotein Group A-B/metabolism
- Humans
- Introns
- Models, Biological
- Molecular Sequence Data
- Nuclear Proteins/metabolism
- Nucleic Acid Conformation
- Protein-Serine-Threonine Kinases/genetics
- RNA Precursors/chemistry
- RNA Splice Sites
- RNA Splicing
- RNA-Binding Proteins
- Recombinant Proteins/genetics
- Ribonucleoprotein, U1 Small Nuclear/genetics
- Ribonucleoprotein, U2 Small Nuclear/genetics
- Sequence Deletion
- Serine-Arginine Splicing Factors
- Spliceosomes/genetics
- Tumor Suppressor Proteins/genetics