Environmental influences on RNA processing: Biochemical, molecular and genetic regulators of cellular response

Abstract

RNA processing has emerged as a key mechanistic step in the regulation of the cellular response to environmental perturbation. Recent work has uncovered extensive remodeling of transcriptome composition upon environmental perturbation and linked the impacts of this molecular plasticity to health and disease outcomes. These isoform changes and their underlying mechanisms are varied-involving alternative sites of transcription initiation, alternative splicing, and alternative cleavage at the 3' end of the mRNA. The mechanisms and consequences of differential RNA processing have been characterized across a range of common environmental insults, including chemical stimuli, immune stimuli, heat stress, and cancer pathogenesis. In each case, there are perturbation-specific contributions of local (cis) regulatory elements or global (trans) factors and downstream consequences. Overall, it is clear that choices in isoform usage involve a balance between the usage of specific genetic elements (i.e., splice sites, polyadenylation sites) and the timing at which certain decisions are made (i.e., transcription elongation rate). Fine-tuned cellular responses to environmental perturbation are often dependent on the genetic makeup of the cell. Genetic analyses of interindividual variation in splicing have identified genetic effects on splicing that contribute to variation in complex traits. Finally, the increase in the number of tissue types and environmental conditions analyzed for RNA processing is paralleled by the need to develop appropriate analytical tools. The combination of large datasets, novel methods and conditions explored promises to provide a much greater understanding of the role of RNA processing response in human phenotypic variation. This article is categorized under: RNA Processing > RNA Editing and Modification RNA Evolution and Genomics > Computational Analyses of RNA RNA Processing > Splicing Mechanisms RNA Processing > Splicing Regulation/Alternative Splicing.