Contact
Positions
Assistant Professor
- Organization:
- West Virginia University School of Medicine
- Department:
- Biochemistry
- Classification:
- Faculty
Publications
Smathers CM and Robart AR. (2020) "Transitions Between the Steps of Forward and Reverse Splicing of Group IIC Introns." RNA. 26(5).
Smathers CM and Robart AR (2019) "The Mechanism of Splicing as Told by Group II Introns: Ancestors of the Spliceosome." BBA gene regul mech. 1862(11).
Geldenhuys WJ, Long TE, Saralkar P, Iwasaki T, Nuñez RAA, Nair RR, Konkle ME, Menze MA, Pinti MV, Hollander JM, Hazlehurst LA, and Robart AR. (2019). "Crystal structure of the mitochondrial protein mitoNEET bound to a benze-sulfonide ligand." Nature Communications Chemistry.
Chan RT, Peters JK, Robart AR, Wiryaman T, Rajashankar KR, Toor N (2018) "Structural basis for the second step of group II intron splicing." Nature Communications. 9(1).
Robart AR, Chan RT, Peters JK, Kanagalaghatta R, Toor N. (2014) "Crystal structure of a eukaryotic group II intron lariat". Nature. 514(7521):193-7.
Chan RT, Robart AR, Kanagalaghatta R, Pyle AM, Toor N. (2012) "Crystal Structure of a Group II Intron in the Pre-Catalytic State." Nature Structural and Molecular Biology. 19(5):555-7.
Robart AR and Collins K (2011) "Human telomerase domain interactions capture DNA for TEN domain-dependent processive elongation." Molecular Cell. 42:308-18.
Robart AR and Collins K (2010) "Ciliate Telomerase RNA Loop IV Nucleotides Promote Hierarchical RNP Assembly and Holoenzyme Stability." RNA. 16(3)
Research Program
RNA Biochemistry / Structural Biology
Research Interests
Although many human diseases are caused by mis-splicing of genes, we still do not fully understand the fundamental mechanisms that drive the function of the splicing machinery or how non-coding RNAs propagate and spread within our genome. Group II introns are mobile genetic elements that are the likely evolutionary ancestors of both the spliceosome and active human retrotransposons. Thus, these ribozymes offer a simplified system to study these fundamental cellular processes. These primitive ribozymes often contain an intron-encoded protein (IEP) that assists splicing to form ribonucleoprotein (RNP) complexes, which act as selfish retroelements that copy and integrate into new genomic locations. In humans, retroelement mobility cause disease by disrupting open reading frames, altering gene regulation, and triggering genomic rearrangements. Long term, we aim to harness the highly sequence specific properties of these movements for biotechnology and gene therapy applications.
The overall goal of our lab is to determine the detailed molecular mechanisms of how intron RNPs form and how these RNPs spread introns to new locations in DNA by combining biochemical and structural biology approaches. Our lab is currently using multiple structural biology methods to understand the structure of the intron ribozyme and the RNP complex, including X-ray crystallography, cryo-electron microscopy (cryo-EM), and small angle X-ray scattering (SAXS). Structural studies are aided and complemented through biochemical, molecular, and bacterial genetic approaches.