Molecular cloning of htra2-beta-1 and htra2-beta-2, two human homologs of tra-2 generated by alternative splicing.

A yeast two-hybrid screen was performed to find new factors involved in pre-mRNA splicing. Using SC35 as a bait, we isolated a human cDNA bearing high homology to the Drosophila transformer-2 (TRA-2) protein. This cDNA was named htra2-beta1. htra2-beta1 is a nuclear protein that colocalizes with SC35 in a speckled pattern. It interacts with several SR proteins tested in yeast. A second form named htra2-beta2 is generated by alternative splicing. This isoform gives rise to a truncated protein without an SR domain. Both isoforms are evenly distributed throughout adult rat tissue. The ratio of these two isoforms changes after stimulation of primary human T-cell and primary rat spleen cell cultures, indicating that alternative splicing is involved in regulation of htra2-beta activity.