PTB/nPTB switch: a post-transcriptional mechanism for programming neuronal differentiation
- Gabriela C. Coutinho-Mansfield1,
- Yuanchao Xue2,
- Yi Zhang2, and
- Xiang-Dong Fu1,2,3
- 1 Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California 92093, USA;
- 2 College of Life Sciences, Wuhan University, Wuhan 430072, People’s Republic of China
This extract was created in the absence of an abstract.
Neuronal differentiation involves extensive reprogramming of gene expression. Many neuronal-specific genes are actively repressed in nonneuronal cells, while many others are induced in response to cell differentiation cues. Together these constitute the transcriptome in neurons to instruct specific neuronal functions (Rosenfeld et al. 2006). The transcriptome in neurons is further diversified by alternative splicing, arising from the expression of a number of neuronal-specific RNA-binding splicing regulators (Black and Grabowski 2003). In this issue of Genes & Development, Boutz et al. (2007b) report a novel switch in the expression of a pair of related splicing regulators that occurs during neuronal differentiation. These proteins, known as polypyrimidine tract-binding proteins (PTB) and neural PTB (nPTB), are structurally and functionally similar, but PTB is widely expressed in nonneuronal cells, and nPTB is restricted to neurons. Remarkably, ∼25% of neuronally induced alternative splicing events detected by mRNA isoform-sensitive splicing arrays are estimated to result from the down-regulation of PTB, and the up-regulation of its neuronal-specific cousin nPTB.
Splicing control by PTB
PTB has been extensively characterized for its sequence-specific binding to CU-rich motifs (Oberstrass et al. 2005), which are frequently part of the 3′ splice site in most constitutively spliced genes. Consequently, PTB binding often antagonizes the function of the essential splicing factor U2AF in the recognition of the 3′ splice site (Singh et al. 1995). PTB-binding sites are also present in many discrete intronic locations to function as cis-acting splicing silencer elements, and PTB has been identified as a negative splicing regulator of many alternative splicing events (Lin and Patton 1995; Chan and Black 1997; Wagner and Garcia-Blanco 2001). Recent biochemical analyses further revealed that PTB could alter the recognition of splicing signals that are far away from its binding sites, indicating an extended competition between the splicing machinery and the PTB-induced splicing silencing …
