Biology Reseach

Plant Genomics Yield Surprising Results

QUESTION How does RNA decay contribute to gene expression? Could the RNA decay rate be regulated on a molecular basis in order to control genetic traits?

Gene expression is typically measured as messenger RNA (mRNA) abundance, and changes in that abundance are usually attributed to transcription, or synthesis, of mRNA inside the cell. However, RNA abundance is also influenced by its disposal, or degradation, but how degradation controls RNA abundance is not well understood.

WHO

“My research uses a plant model, Arabidopsis thaliana, a small mustard plant, and we found that mutants with defects in mRNA decapping proteins experienced abnormal cell growth,” says Leslie Sieburth, Professor of Biological Sciences at the U.

“Our curiosity about why the mutants showed such poor growth led us to discover another mRNA decay enzyme, which we call SOV. We noted in our publication, in 2010, that most eukaryotic genomes encode a very similar protein, including humans,” says Sieburth.

A few years later, in 2013, scientists studying a human disorder called Perlman syndrome discovered that it was caused by mutations in the same gene. The gene, SOV, is known as DIS3L2 in humans.

Perlman syndrome is a genetic disorder associated with overgrowth in the size of the body or a body part of infants. The condition is almost always fatal prior to birth. The disorder has been grouped with Renal cell carcinoma and an increased risk for Wilms tumor.

Starting in 2014, Sieburth investigated how mRNA decapping and SOV/DIS3L2 contribute to decay of all mRNAs using genome-wide approaches. “A fruitful collaboration with Fred Adler, a professor of biology and mathematics at the U, one of his graduate students, Katrina Johnson, and my postdoc Reed Sorenson, identified the decay rates of more than 17,000 mRNAs, and the contributions from decapping and SOV/DIS3L2,” says Sieburth.

One unexpected discovery was that the mRNAs that decay the fastest use the mRNA decapping pathway. A second discovery was that Arabidopsis mutants lacking an active SOV initiate a feedback