GRO-seq analysis of liver gene transcription in hibernating 13-lined ground squirrels

ABSTRACT: Hibernators dramatically lower metabolism to save energy while fasting for months. Prolonged fasting challenges metabolic homeostasis, yet small-bodied hibernators emerge each spring ready to resume all aspects of active life, including immediate reproduction. The liver is the body’s metabolic hub, processing and detoxifying macromolecules to provide essential fuels to brain, muscle and other organs throughout the body. Here we quantify changes in liver gene expression using RNA-seq to measure the steady-state transcriptome and GRO-seq to measure transcription across several distinct physiological states of hibernation in 13-lined ground squirrels. Our data capture key timepoints in both the seasonal and torpor-arousal cycles of hibernation. Strong positive correlation between transcription and the transcriptome indicates that transcriptional control dominates the known seasonal reprogramming of metabolic gene expression in liver for hibernation. During the torpor-arousal cycle, however, discordance develops between transcription and the steady-state transcriptome by at least two mechanisms: 1) although not transcribed during torpor, some liver transcripts are unusually stable, consistent with data from other tissues; and 2) unexpectedly, on some genes, we document continuing, slow elongation with a failure to terminate transcription across the torpor bout. While the steady-state RNAs corresponding to these readthrough transcripts did not increase during torpor, they did increase shortly after rewarming despite then low transcription. Both of these mechanisms assure the availability of functional transcripts immediately upon rewarming. Integration of transcriptional, post-transcriptional and RNA stability control mechanisms, all demonstrated in these data, likely initiate a serial gene expression program across the short euthermic period that restores the tissue and prepares the animal for the next bout of torpor.

ORGANISM(S): Ictidomys tridecemlineatus

PROVIDER: GSE166370 | GEO | 2021/05/10

REPOSITORIES: GEO