How does Tra2β protein regulate tissue-specific RNA splicing?

The splicing regulator protein Tra2 beta is conserved between humans and insects and is essential for mouse development. Recent identification of physiological RNA targets has started to uncover molecular targets and mechanisms of action of Tra2 beta. At a transcriptome-wide level, Tra2 beta protein binds a matrix of AGAA-rich sequences mapping frequently to exons. Particular tissue-specific alternatively spliced exons contain high concentrations of high scoring Tra2 beta-binding sites and bind Tra2 beta strongly in vitro. These top exons were also activated for splicing inclusion in cellulo by co-expression of Tra2 beta protein and were significantly down-regulated after genetic depletion of Tra2 beta. Tra2 beta itself seems to be fairly evenly expressed across several different mouse tissues. In the present paper, we review the properties of Tra2 beta and its regulated target exons, and mechanisms through which this fairly evenly expressed alternative splicing regulator might drive tissue-specific splicing patterns.