Furneaux Lab

• Lab Members
• Research Interests
• Research Projects
• Publications

Lab Members

Research Interests

[back to top]

Research Projects

Currently, projects are available in three areas.

Studies on the Regulation of mRNA Stability
Many mRNAs contain cis-acting elements that direct their rapid turnover. The first cis-acting sequence to be described was the U-rich or Shaw-Kamen element. In unstimulated cells, mRNAs that contain U-rich elements rapidly disappear. Upon appropriate stimulation, a specific mRNA/protein complex is formed, decay is blocked, and a rapid rise in the steady state level of the mRNA ensues. We have shown that a family of mRNA binding proteins stabilizes such mRNAs. We first discovered these proteins as human tumor antigens that elicit autoimmune neurological disorders. These RNA binding proteins are called the Elav-like proteins because of their homology to Elav, a Drosophila protein that regulates neuronal differentiation. The way in which cellular signals activate the binding of the Elav-like proteins to mRNA is one focus of our future efforts. To more clearly understand how the Elav-like proteins work it is critical to understand the specific mRNA decay mechanism that is directed by the Shaw-Kamen element. Therefore, we are also studing the mechanism of action of proteins such as TTP and BRF, which specifically direct the degradation of U-rich element containing mRNAs.

The Mechanism of Action of miRNAs
Micro RNAs, or miRNAs are, small single stranded non-coding RNAs that silence gene expression by directly annealing to a complementary target mRNA. Recently, we have reconstituted the action of miRNAs in a cell-free system using extracts from human cells. We have found that the let-7 miRNA directs the cleavage of its lin-41 mRNA target. Future studies will focus on how miRNAs catalyze the cleavage of mRNA and the identification of the protein components of the miRNA/mRNA complex.

A New mRNA Splicing Pathway
Recently, it has become clear that mRNA may be spliced a by non-spliceosommal mechanism. In mammals and yeast, the unfolded protein response directs the alternative splicing of mRNA. In this pathway, the mRNA is cleaved by a specific endonuclease (the IREp protein in yeast) and is believed to be spliced by a putative RNA ligase that requires 2'3'cylic phosphate termini. Our aim is to identify this novel RNA ligase in mammalian cells.

[back to top]