2021 Annual Meeting Report: Roll of the Splice: Understanding the Role of Alternative Splicing in Predictive Toxicology and Medicine

By Sarah Carratt posted 04-01-2021 13:45


Alternative splicing events can lead to differential responses to xenobiotics because of the modified synthesis of proteins. In other words, how each new protein variant is able to contribute to metabolism and disease progression is a roll of the dice.

In the Workshop Session “Revising Biology: Alternative Splicing in Toxicology” during the SOT 60th Annual Meeting and ToxExpo, Drs. Annalora, Wright, and Cardoso presented their research on the mechanisms by which alternative splicing alters wild-type protein functions. Among other things, this research may allow for splicing variants to be used as novel biomarkers of exposures and predictors of prognosis.

To highlight how important alternative splicing can be in the process of xenobiotic metabolism, Dr. Annalora offered the example of how splicing variants of P450 enzymes can interfere with the ability of the enzymes to recognize xenobiotics. In his talk, he discussed how both calcifediol (vitamin D3) and the toxicant benzo(a)pyrene are metabolized by P450s, and how alternative splicing can change the fate of the compound. In terms of steroid structure, benzo(a)pyrene looks similar to calcifediol. P450s that are basally expressed to recognize each of these xenobiotics may be alternatively spliced in ways that interfere with the ability of a P450 to recognize the difference between nutrition and pollution.

Alternative splicing is an interesting field of study. In addition to the identification of biomarkers, alternative splicing can help to elucidate the heterogenous responses of individuals to environmental exposures and therapeutic treatments.

The role of alternative splicing has been underappreciated in toxicology because of the detection limits of current RNA and protein analysis methods. However, the panelists in this session were very optimistic. In the words of Dr. Annalora, “In the next decade, we will start to get a much better understanding of the interindividual differences in gene splicing that underlie disease states, and chemical exposures, which will create improved diagnostics and smarter drugs that can address personalized disorders.”

This blog was prepared by an SOT Reporter and represents the views of the author. SOT Reporters are SOT members who volunteer to write about sessions and events in which they participate during the SOT Annual Meeting and ToxExpo. SOT does not propose or endorse any position by posting this article. If you are interested in participating in the SOT Reporter program in the future, please email Giuliana Macaluso.

Sessions delivered during the 2021 SOT Annual Meeting and ToxExpo will be available on the Virtual Meeting Platform on demand to registrants through May 31, 2021.