Hi I’m Zhaiyi. I joined Stefan’s group in November 2002 as a Ph.D. student. My major project is to characterize the ubiquitously expressed nuclear protein YT521-B.YT521-B localizes to a novel subnuclear compartment: the YT bodies which appear at the beginning of S-phase in the cell cycle and disperse during mitosis. YT521-B interacts with several splicing factors, such as Sam68, rSAF-B and hnRNPG. It alters the splice site selection and regulates alternative exon usage in a concentration-dependent manner. YT521-B is tyrosine phosphorylated by certain non receptor tyrosine kinases. Tyrosine phosphorylation causes dispersion of YT521-B from YT bodies to the nucleoplasm and thus abolishes the ability of YT521-B to change alternative splice sites.

YT521-B does not belong to any of the known splicing factor families. It contains several functional domains: pro-rich domain, ER-rich domain and YTH domain. The pro-rich domain might play an important role in the protein-protein interaction with SH3 domain containing protein. The ER-rich domain mediates the interaction with SR proteins. The YTH (YT521-B homology) domain is a novel domain identified in the BLAST searches. This domain is remarkably conserved across a wide species range. The putative secondary structure indicates that the YTH domain consists of four alpha-helices and six beta-sheets; furthermore the conservation of aromatic residues located in the beta-strands is reminiscent of the RNA recognition motif (RRM) domain.

In order to characterize the binding property of YTH domain, in vitro SELEX, gel shift experiment and in vivo functional splicing assay were performed and showed that YTH domain binds to a 6 nucleotides degenerated motif and therefore influences alternative exon usage.

eMail Zhaiyi Zhang