Integration of Nascent Transcriptomes and Cross-Species Atlases Reveals Evolutionary Barriers in Transcriptional Kinetics During Mammalian Hibernation

Mammalian hibernation requires extensive metabolic remodeling, but traditional transcriptomic approaches cannot distinguish between mRNA synthesis and degradation, leaving the evolutionary barriers governing its transcriptional control unclear. To address this, we integrated nascent (GRO-seq) and steady-state (RNA-seq) transcriptomes from the 13-lined ground squirrel (Ictidomys tridecemlineatus) with multi-species liver data from the Siberian chipmunk and Syrian hamster. By constructing an atlas of 78 core consensus genes and applying the stability index (SI), betweenness centrality (BC), and network clustering, we identified two complementary regulatory modes: a Triple Conserved backbone centered on ACLY and ATF4, alongside “Species-Specific Synergy” modules involving ADCY6 and EGR1. Kinetic analysis revealed distinct transcriptional-decoupling patterns (SLC2A1 showed a transcript stabilization pattern with SI = 2.01, whereas ID2 exhibited an uncompensated transcriptional induction with SI = −1.87). Network analysis placed ADCY6 (BC = 0.3356) as a central hub linking signal transduction to metabolic remodeling, and MCODE clustering further resolved three functional modules enriched for metabolic regulation, RNA processing, and lipid homeostasis. Together, these results suggest that hibernation does not simply suppress transcription but instead operates as a dynamic balance system, where specific genes rely on post-transcriptional stability compensation under sustained transcriptional stress. These findings offer a cross-species view of how mammals achieve metabolic robustness and may inform cryopreservation strategies in translational contexts.