Lost in Translation: Exploring microRNA Biogenesis and Messenger RNA Fate in Anoxia-Tolerant Turtles

Abstract

Red-eared slider turtles face natural changes in oxygen availability throughout the year. This includes long-term anoxic brumation where they reduce their metabolic rate by ~90% for months at a time, which they survive without apparent tissue damage. This metabolic rate depression (MRD) is underlaid by various regulatory mechanisms, including messenger RNA (mRNA) silencing via microRNA (miRNA), leading to mRNA decay or translational inhibition in processing bodies (P-bodies) and stress granules. Regulation of miRNA biogenesis was assessed in red-eared slider turtle liver and skeletal muscle via immunoblotting. Hepatic miRNA biogenesis was downregulated in early processing steps, while later steps were upregulated. These contradictory findings indicate either overall decreased miRNA biogenesis, or increased biogenesis if sufficient pre-miRNA stores were produced in early anoxia. Conversely, muscle showed clear upregulation of multiple biogenesis steps indicating increased miRNA production. Additionally, immunoblotting indicated that P-bodies may be favoured by the liver for mRNA storage/decay during reoxygenation with a strong suppression of stress granule proteins in anoxia and reoxygenation. Muscle however showed downregulation of P-bodies during anoxia and reoxygenation, and upregulation of stress granules for mRNA storage during reoxygenation. This study advances our understanding of how these champion anaerobes regulate miRNA biogenesis to alter miRNA expression and mRNA fate during prolonged anoxia.

Torpor‐responsive microRNAs in the heart of the Monito del monte, Dromiciops gliroides

“…35,36 Many previous studies have implicated differential miRNA regulation and expression during MRD in various animals exposed to a variety of environmental stresses. [37][38][39][40][41][42][43][44][45] These findings underscore the critical role miRNAs play in regulating gene expression to facilitate stress tolerance across vast species.…”

“…Additionally, miRNA expression is known to change in response to external stimuli, including extreme environmental stress 35,36 . Many previous studies have implicated differential miRNA regulation and expression during MRD in various animals exposed to a variety of environmental stresses 37–45 . These findings underscore the critical role miRNAs play in regulating gene expression to facilitate stress tolerance across vast species.…”