WT1 interacts with the splicing factor U2AF65 in an isoform-dependent manner and can be incorporated into spliceosomes

AUTOR(ES)

Davies, Rachel C.

FONTE

Cold Spring Harbor Laboratory Press

RESUMO

WT1 is essential for normal kidney development, and genetic alterations are associated with Wilms’ tumor, Denys Drash (DDS), and Frasier syndromes. Although generally considered a transcription factor this study has revealed that WT1 interacts with an essential splicing factor, U2AF65, and associates with the splicing machinery. WT1 is alternatively spliced and isoforms that include three amino acids, KTS, show stronger interaction with U2AF65 in vitro and better colocalization with splicing factors in vivo. Interestingly a mutation associated with DDS enhanced both −KTS WT1 binding to U2AF65 and splicing-factor colocalization. These data illustrate the functional importance of WT1 isoforms and suggest that WT1 playsa role in pre-mRNA splicing.

Documentos Relacionados

• Evidence for Substrate-Specific Requirement of the Splicing Factor U2AF35 and for Its Function after Polypyrimidine Tract Recognition by U2AF65
• A putative homology of U2AF65 in S. cerevisiae.
• A putative homolog of U2AF65 in S. cerevisiae.
• Human Immunodeficiency Virus Type 1 hnRNP A/B-Dependent Exonic Splicing Silencer ESSV Antagonizes Binding of U2AF65 to Viral Polypyrimidine Tracts
• A cooperative interaction between U2AF65 and mBBP/SF1 facilitates branchpoint region recognition