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Polypyrimidine tract binding protein regulates alternative splicing of an aberrant pseudoexon in NF1.

Authors :
Raponi, Michela
Buratti, Emanuele
Llorian, Miriam
Stuani, Cristiana
Smith, Christopher W. J.
Baralle, Diana
Source :
FEBS Journal; Dec2008, Vol. 275 Issue 24, p6101-6108, 8p, 6 Black and White Photographs, 1 Diagram
Publication Year :
2008

Abstract

In disease-associated genes, understanding the functional significance of deep intronic nucleotide variants represents a difficult challenge. We previously reported that an NF1 intron 30 exonization event is triggered from a single correct nomenclature is ā€˜c.293-279 A>Gā€™ mutation [Raponi M, Upadhyaya M & Baralle D (2006) Hum Mutat 27, 294ā€“295]. In this paper, we investigate which characteristics play a role in regulating inclusion of the aberrant pseudoexon. Our investigation shows that pseudoexon inclusion levels are strongly downregulated by polypyrimidine tract binding protein and its homologue neuronal polypyrimidine tract binding protein. In particular, we provide evidence that the functional effect of polypyrimidine tract binding protein is proportional to its concentration, and map the cis-acting elements that are principally responsible for this negative regulation. These results highlight the importance of evaluating local sequence context for diagnostic purposes, and the utility of developing therapies to turn off activated pseudoexons. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
1742464X
Volume :
275
Issue :
24
Database :
Complementary Index
Journal :
FEBS Journal
Publication Type :
Academic Journal
Accession number :
35394101
Full Text :
https://doi.org/10.1111/j.1742-4658.2008.06734.x