global study of RNA degradation using F1 hybrid mice

Cellular RNA abundance is determined by both RNA transcription and decay. Therefore, change in RNA abundance, which can drive phenotypic diversity between different species, could arise from genetic variants affecting either process. However, previous studies in the evolution of RNA expression have been largely focused on transcription. Here, to globally investigate the effects of cis-regulatory divergence on RNA decay in mammals for a first time, we quantified allele-specific differences in RNA decay rates (ASD) in an F1 hybrid mouse. Out of 8,815 genes with sufficient data, we identified 621 genes exhibiting significant cis-divergence. Systematic analysis of these genes revealed that the genetic variants affecting microRNA binding and RNA secondary structures contribute to the observed divergences. Finally, we demonstrated that whereas the divergences in RNA abundance were predominantly determined by allelic differences in RNA transcription (AST); most genes with significant ASD did not exhibit significant difference in RNA abundance. For these genes, the apparently compensatory effect between AST and ASD suggests changes in RNA decay could serve as important means to stabilize RNA abundances during mammalian evolution.