Abstract
Mammalian hibernators survive low body temperatures, ischemia–reperfusion, and restricted nutritional resources via global reductions in energy-expensive cellular processes and selective increases in stress pathways. Consequently, studies that analyze hibernation uncover mechanisms which balance metabolism and support survival by enhancing stress tolerance. We hypothesized processing factors that influence messenger ribonucleic acid (mRNA) maturation and translation may play significant roles in hibernation. We characterized the amino acid sequences of three RNA processing proteins (T cell intracellular antigen 1 (TIA-1), TIA1-related (TIAR), and poly(A)-binding proteins (PABP-1)) from thirteen-lined ground squirrels (Ictidomys tridecemlineatus), which all displayed a high degree of sequence identity with other mammals. Alternate Tia-1 and TiaR gene variants were found in the liver with higher expression of isoform b versus a in both cases. The localization of RNA-binding proteins to subnuclear structures was assessed by immunohistochemistry and confirmed by subcellular fractionation; TIA-1 was identified as a major component of subnuclear structures with up to a sevenfold increase in relative protein levels in the nucleus during hibernation. By contrast, there was no significant difference in the relative protein levels of TIARa/TIARb in the nucleus, and a decrease was observed for TIAR isoforms in cytoplasmic fractions of torpid animals. Finally, we used solubility tests to analyze the formation of reversible aggregates that are associated with TIA-1/R function during stress; a shift towards the soluble fraction (TIA-1a, TIA-1b) was observed during hibernation suggesting enhanced protein aggregation was not present during torpor. The present study identifies novel posttranscriptional regulatory mechanisms that may play a role in reducing translational rates and/or mRNA processing under unfavorable environmental conditions.
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Acknowledgments
We would like to thank Dr. J.M. Hallenbeck and Dr. D.C. McMullen (NINDS, NIH, Bethesda) for providing the tissue samples for this study. Thanks also to J.M. Storey for editorial review of the manuscript. Research was supported by a grant from the Canadian Institute of Health Research (CIHR) to SL, a discovery grant from the Natural Sciences and Engineering Research Council (NSERC) of Canada to KBS, and the Canada Research Chairs program. SNT held an NSERC PGSD scholarship.
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Tessier, S.N., Audas, T.E., Wu, CW. et al. The involvement of mRNA processing factors TIA-1, TIAR, and PABP-1 during mammalian hibernation. Cell Stress and Chaperones 19, 813–825 (2014). https://doi.org/10.1007/s12192-014-0505-8
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DOI: https://doi.org/10.1007/s12192-014-0505-8