mRNA Stability and Polysome Loss in Hibernating Arctic Ground Squirrels (Spermophilus parryii)

Abstract

All small mammalian hibernators periodically rewarm from torpor to high, euthermic body temperatures for brief intervals throughout the hibernating season. The functional significance of these arousal episodes is unknown, but one suggestion is that rewarming may be related to replacement of gene products lost during torpor due to degradation of mRNA. To assess the stability of mRNA as a function of the hibernation state, we examined the poly(A) tail lengths of liver mRNA from arctic ground squirrels sacrificed during four hibernation states (early and late during a torpor bout and early and late following arousal from torpor) and from active ground squirrels sacrificed in the summer. Poly(A) tail lengths were not altered during torpor, suggesting either that mRNA is stabilized or that transcription continues during torpor. In mRNA isolated from torpid ground squirrels, we observed a pattern of 12 poly(A) residues at greater densities approximately every 27 nucleotides along the poly(A) tail, which is a pattern consistent with binding of poly(A)-binding protein. The intensity of this pattern was significantly reduced following arousal from torpor and undetectable in mRNA obtained from summer ground squirrels. Analyses of polysome profiles revealed a significant reduction in polyribosomes in torpid animals, indicating that translation is depressed during torpor.Hibernation in mammals is an energy-conserving strategy involving physiological and behavioral accommodations to low body temperature and low metabolic rate for extended, but not indefinite, periods (12). Hibernation involves a cyclic up-and down-regulation of metabolism (36). The arctic ground squirrel (Spermophilus parryii) illustrates an extreme example of hibernation under adverse conditions.

Elevated expression of protein biosynthesis genes in liver and muscle of hibernating black bears (Ursus americanus)

“…There are several lines of evidence for significant depression of protein biosynthesis in small hibernators during steady-state torpor. Evidence for translational suppression was provided by measuring conversion rates of radioactively labeled amino acids and examining tissue extracts for their ability to support translation in vitro and detecting significant loss of polyribosomes during torpor (7,21). Evidence for translational suppression during torpor at the transcriptional level was also obtained in a recent study (43) showing coordinated underexpression of protein biosynthesis genes in brown adipose tissue of hibernating arctic ground squirrels.…”

Regulation of hypometabolism: insights into epigenetic controls

“…Typically, poly(A) tail lengths shorten over time and when they get too short, the mRNA is enzymatically degraded. However, this did not happen in ground squirrel liver during torpor; mean lengths of poly(A) tails did not change over prolonged torpor and were not different from those in summer euthermic animals (Knight et al, 2000). As torpor duration increased, peaks representing overabundant poly(A) tail lengths appeared with a size distribution that indicated that protection was applied every 27 nt.…”

“…The authors proposed that this may be a fast and energetically efficient way to respond to a huge reduction in the demand for protein synthesis while still retaining the capacity to reactivate this ATP-expensive cell function immediately upon arousal. Multiple studies have documented polysome dissociation during mammalian hibernation (Whitten et al, 1970;Frerichs et al, 1998;Knight et al, 2000;Hittel and Storey, 2002) and other forms of hypometabolism (e.g. hypoxia, anoxia), with an opposite increase in monosomes and a sequestering of most mRNA transcripts into monosome and/or ribonuclear protein fractions (reviewed in Storey and Storey, 2004).…”

Hibernating above the permafrost: effects of ambient temperature and season on expression of metabolic genes in liver and brown adipose tissue of arctic ground squirrels

“…During torpor, global suppression of mRNA transcription occurs (Van Breukelen and Martin, 2002;Morin and Storey, 2006). Furthermore, reversible phosphorylation of ribosomal initiation and elongation factors along with polysome disassociation results in global suppression of mRNA translation during torpor in brain, liver and kidney (Frerichs et al, 1998;Knight et al, 2000;Van Breukelen and Martin, 2001;Hittel and Storey, 2002). Thus, arctic ground squirrels would be unable to transcribe mRNA and translate proteins to respond to an increase in metabolic load associated with decreases in T a that occurred within torpor bouts, which can last 24days.…”