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The alternative splicing factors PTB and nPTB control exon repression during neuronal development
Author(s) -
Black Douglas L,
Li Qin,
Sharma Shalini
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.305.1
Subject(s) - exon , rna splicing , alternative splicing , polypyrimidine tract , biology , exonic splicing enhancer , polypyrimidine tract binding protein , exon skipping , rna binding protein , microbiology and biotechnology , splicing factor , genetics , gene , rna
The polypyrimidine tract binding protein (PTB) represses the inclusion of many neuron‐specific exons. Upon neuronal differentiation, cells lose PTB and upregulate a neuron‐specific paralog, nPTB. The switch in expression from PTB to nPTB controls a program of alternative splicing in the developing brain involving exons that affect proteins involved in cytoskeletal assembly, protein trafficking, synapse formation, and neuronal survival. The role of this splicing program in neuronal development is not well understood. To investigate the in vivo function of nPTB and its targets in neurons, we generated a conditional knockout mouse of nPTB, using the Cre/Lox methodology. Splice‐junction microarray analysis and RT‐PCR identified many alternatively spliced exons that are misregulated in nPTB knockout brains. We are examining the cause of neuronal death in these mice. We are also studying the mechanism of splicing regulation by PTB in an in vitro splicing system. PTB binds to sequences flanking an exon to prevent its splicing in non‐neuronal cell extracts. We find that PTB blocks splice site pairing interactions required for formation of the spliceosomal B complex. We are currently examining the interactions of PTB that may mediate this effect on splicing complex assembly.