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A study of gene expression in leukemia cells has identified an RNA binding protein that plays an important role in driving the development of cancer. The protein is normally active in fetal tissue and switched off in adults, but it is reactivated in some cancer cells. This expression pattern makes it an attractive target for cancer-fighting drugs, because blocking its activity is unlikely to cause serious side effects.

The new study, published March 14 in the Journal of Clinical Investigation, focused on a particularly aggressive form of B-cell acute lymphoblastic leukemia (B-ALL), the most prevalent type of leukemia in children and young adults. A team led by scientists at UC Santa Cruz and UCLA found an overabundance of the RNA binding protein known as IGF2BP3 in the cancer cells of this subset of B-ALL patients.

“This protein, IFG2BP3, has been correlated with many types of malignancies and with the worst prognoses,” said coauthor Jeremy Sanford, associate professor of molecular, cell, and developmental biology at UC Santa Cruz. “What is exciting about this study is that it goes beyond correlation and shows causation, because we demonstrated for the first time that aberrant expression of this protein is sufficient to induce pathology.”

The researchers identified genes that are directly regulated by this RNA binding protein, and many of them turn out to be oncogenes that have already been implicated in cancer. In particular, the protein enhances the expression of a well-characterized oncogene called MYC, which in turn regulates a large number of genes involved in cell proliferation.

Compared to other proteins involved in regulating gene activity, RNA binding proteins have not been well studied. When a gene is turned on or “expressed,” an RNA copy is made of the gene’s DNA sequence, and the genetic code carried by this “messenger RNA” is then translated into a protein that carries out some cellular function. Many factors are involved in controlling which genes get transcribed into messenger RNA and when, but RNA binding proteins interact with the messenger RNA itself to regulate gene expression after transcription has occurred. Scientists are only beginning to unravel the complexity of this post-transcriptional regulation of gene expression.

In the case of IGF2BP3 and B-cell leukemia, the overall effect of the RNA binding protein is to promote the proliferation of B cells by shifting the expression of a large number of genes, Sanford said.

Sourced through Scoop.it from: news.ucsc.edu

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