Post-transcriptional regulation supports the homeostatic expression of mature RNA

Gene expression regulation is a sophisticated, multi-stage process, and its robustness is critical to normal cell function and the survival of an organism. Previous studies indicate that differential gene expression at the RNA level is typically attenuated at the protein level through translational regulation. However, how post-transcriptional regulation (PTR) influences expression change during the RNA maturation process remains unclear. In this study, we investigated this by quantifying the magnitude of expression change in precursor RNA and mature RNA across a vast range of different biological conditions. We analyzed bulk tissue RNA sequencing data from 4689 samples, including healthy and diseased tissues from human, chimpanzee, rhesus macaque, and murine sources. We demonstrated that PTR tends to support homeostatic expression of mature RNA by amplifying normal tissue-specific expression of precursor RNA, while reducing expression change of precursor RNA in disease contexts. Our study provides insight into the general influence of PTR on gene expression homeostasis. Our analysis also suggests that intronic reads in RNA-seq studies may contain under-utilized information about disease associations. Additionally, our findings may assist in identifying new disease biomarkers and more effective ways of altering gene expression as a therapeutic strategy.