How does Tra2ß protein regulate tissue-specific RNA splicing?

ABSTRACT

The splicing regulator protein Tra2ß 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 Tra2ß. At a transcriptome-wide level, Tra2ß protein binds a matrix of AGAA-rich sequences mapping frequently to exons. Particular tissue-specific alternatively spliced exons contain high concentrations of high scoring Tra2ß-binding sites and bind Tra2ß strongly in vitro. These top exons were also activated for splicing inclusion in cellulo by co-expression of Tra2ß protein and were significantly down-regulated after genetic depletion of Tra2ß. Tra2ß itself seems to be fairly evenly expressed across several different mouse tissues. In the present paper, we review the properties of Tra2ß and its regulated target exons, and mechanisms through which this fairly evenly expressed alternative splicing regulator might drive tissue-specific splicing patterns.