MicroRNAs regulate survival in oxygen-deprived environments

Abstract

Some animals must endure prolonged periods of oxygen deprivation to survive. One such extreme model is the Northern Crayfish (Orconectes virilis), that regularly survives year-round hypoxic and anoxic stresses in its warm stagnant summer waters and in its cold, ice-locked winter waters. To elucidate the molecular underpinnings of anoxia-resistance in this natural model, we surveyed the expression profiles of 76 highly-conserved microRNAs in crayfish hepatopancreas and tail muscle from normoxic, acute 2hr anoxia, and chronic 20hr anoxia exposures. MicroRNAs are known to regulate a diverse array of cellular functions required for environmental stress adaptations, and here we explore their role in anoxia tolerance. The tissue-specific anoxia responses observed herein, with 22 anoxia-responsive microRNAs in hepatopancreas and only 4 changing microRNAs in muscle, suggest that microRNAs facilitate a reprioritization of resources to preserve crucial organ functions. Bioinformatic microRNA target enrichment analysis predicted that the anoxia-downregulated microRNAs in hepatopancreas targeted hippo-signalling, suggesting that cell proliferation and apoptotic signalling are highly regulated in this liver-like organ during anoxia. Compellingly, miR-125-5p, miR-33-5p, and miR-190-5p, all known to target the master regulator of oxygen deprivation responses HIF1 (Hypoxia Inducible Factor-1), were anoxia-downregulated in hepatopancreas. The anoxia-increased transcript levels of the oxygen dependent subunit HIF1α, highlight a potential critical role for miRNA-HIF targeting in facilitating a successful anoxia response. Studying the cytoprotective mechanisms in place to protect against the challenges associated with surviving in oxygen-poor environments is critical to elucidating microRNAs’ vast and substantial role in the regulation of metabolism and stress in aquatic invertebrates.