The phenomenon of mRNA trans-ligation is a poorly understood process in need of novel experimental techniques and insight. This proposal will study mRNA trans-ligation in human cancer cells that was discovered as a response to treatment with a clinically relevant ribonuclease. The extent of mRNA trans- ligation induced by ribonucleases will be characterized by RNA sequencing techniques. An enzyme hypothesized to be responsible for the observed mRNA ligation will be characterized kinetically and mechanistically. A combination of cellular studies and in vitro characterizations of mRNA ligation will bring to light important details about this uncharacterized physiological process. A fundamental understanding of mRNA trans-ligation is likely to lead to an understanding of various normal physiological and disease processes.
The proposed research will investigate the uncharacterized phenomenon of mRNA trans-ligation. A fundamental understanding of this process will be important to understand the role mRNA trans-ligation plays in both normal physiological and various disease processes. Characterization of the enzyme involved in this process will facilitate the design of inhibitors that specifically target mRNA trans-ligation.
|Desai, Kevin K; Beltrame, Amanda L; Raines, Ronald T (2015) Coevolution of RtcB and Archease created a multiple-turnover RNA ligase. RNA 21:1866-72|
|Desai, Kevin K; Bingman, Craig A; Cheng, Chin L et al. (2014) Structure of RNA 3'-phosphate cyclase bound to substrate RNA. RNA 20:1560-6|
|Desai, Kevin K; Cheng, Chin L; Bingman, Craig A et al. (2014) A tRNA splicing operon: Archease endows RtcB with dual GTP/ATP cofactor specificity and accelerates RNA ligation. Nucleic Acids Res 42:3931-42|
|Desai, Kevin K; Bingman, Craig A; Phillips Jr, George N et al. (2013) Structures of the noncanonical RNA ligase RtcB reveal the mechanism of histidine guanylylation. Biochemistry 52:2518-25|