Cutting edge

In normal cells, mRNA splicing can edit a single sequence of genetic material in various ways, making transcripts for many different proteins.

Increasingly, studies have shown that aberrant splicing induces widespread transcript changes in associated cancers, noted Angela Brooks, UC Santa Cruz assistant professor of biomolecular engineering. For the first time, in a study published in Cancer Cell, Brooks and her colleagues linked one specific change in the splicing complex to a functional effect.

The SF3B1 mutation alters a single protein in the splicing complex. With Brooks’ expertise in computational analysis of mRNA transcripts, researchers uncovered an SF3B1-induced change in the DVL2 gene, which, in turn, activated a cancer pathway previously known as a factor in chronic lymphocytic leukemia, but not known to be activated by SF3B1.

Now Brooks is developing high-throughput assays to simultaneously test the functional effects of hundreds of mutated RNA transcripts. She’s also focused on better understanding the splicing mechanism.

“Even in normal tissue we get different splicing patterns and we don’t really have a grasp of what’s happening,” she said.