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A splice of the action: Translational role for WT1 isoform

In the June 15th issue of G&D, Dr. Marie-Louise Hammarskjold (UVA) and colleagues lend new insight into the function of the Wilms' Tumor 1 tumor suppressor. The Wilms' Tumor 1 (WT1) protein is important to both normal and pathological human development, with known roles in kidney and urogenital formation as well as several human cancers.

Dr. Hammarskjold and colleagues reveal that WT1 works not only at the transcriptional level, but also at the post-transcriptional level to regulate gene expression. The WT1 gene encodes two major alternatively spliced protein isoforms: WT1(+KTS) and WT1(-KTS). While WT1(-KTS) has an established role as a DNA-binding transcription factor, the function of WT1(+KTS) has been elusive.

Dr. Hammarskjold's team now show that WT1(+KTS) promotes translation of target mRNAs by aiding in the transport and cytoplasmic stability of unspliced, intron-containing mRNA. Dr. Hammarskjold explains that "the general impact of this study is that it highlights the links that exist between transcription and post-transcriptional gene regulation and the importance of alternative splicing. We hope that these results will stimulate further studies to identify genes that are regulated by WT1 at the translational level and the role that this type of regulation plays in normal development and disease."


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Source:Cold Spring Harbor Laboratory


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