Research Program

In the Rader Lab we seek to develop tools that will allow us to investigate the biological role of pre-mRNA splicing from an evolutionary perspective. We are addressing such questions as: How does splicing help cells adapt to environmental changes? What are the pressures that lead to intron loss in certain lineages? And what is the minimal set of splicing machinery necessary for cell viability?

Cyanidioschyzon merolae
In 2015 we reported that C. merolae completely lacks the U1 particle that in other organisms is responsible for recognition of the 5' splice site of introns (Stark 2015). This red alga lives in biofilms in volcanic hot springs at temperatures up to 60 C and pH as low as 0.05. It tolerates high levels of heavy metals. Most interestingly for us, it has lost all but 27 of the thousands of introns that its ancestor harbored in its genome.
The Biological Function of Introns
We have taken a number of approaches to investigate whether the remaining 27 introns in C. merolae have an important biological function. Deletion of individual introns, or up to four simultaneously, has had little to no effect. We have subjected the algae to a variety of stress conditions and measured whether splicing changes in response using RNA sequencing and proteomics. And we are testing various models for how introns are recognized without the U1 snRNP.
Spliceosome Structures
To better understand how splicing works at the atomic level, we collaborate with colleagues around the world to identify components of splicing complexes and determine their 3-dimensional structures (Reimer 2017; Garside 2019; Black 2016).