Potential role for microRNA in regulating hypoxia-induced metabolic suppression in jumbo squids

Abstract

At night, Humboldt squid (Dosidicus gigas) rise to the ocean's surface to feed, but come morning, they descend into the ocean's oxygen minimum zone where they can avoid predators but must deal with severe hypoxia, high pressure, and very cold water. To survive this extreme environment, squid use various adaptations to enter a hypometabolic state characterized by metabolic rate suppression by 35-52%, relative to normoxic conditions. The molecular mechanisms facilitating this metabolic flexibility have yet to be elucidated in hypometabolic squid. Herein, we report the first investigation of the role of microRNAs, a rapid and reversible post-transcriptional master regulator of virtually all biological functions, in cephalopods. We examined expression levels of 39 highly-conserved invertebrate microRNAs in D. gigas brain, mantle muscle, and branchial heart, comparing hypoxic and normoxic conditions. Hypoxia-inducible microRNAs are potentially involved in facilitating neuroprotection, anti-apoptosis, and regenerative mechanisms in brain; inhibiting apoptosis and cell proliferation while conserving energy in heart; and limiting damage by reactive oxygen species and apoptosis in muscle. Rather than orchestrate global metabolic rate depression, the majority of hypoxia-inducible microRNAs identified are involved in promoting cytoprotective mechanisms, suggesting a regulatory role for microRNA in hypoxic marine invertebrates that sets the stage for mechanistic analyses.

MicroRNAs regulate survival in oxygen-deprived environments

“…The ubiquitous role of miRNAs as regulators of cellular functions is widely accepted but their role in the stress response in naturally anoxia-tolerant organisms has not been deeply explored. Although exact mechanisms have yet to be deciphered, recent research has linked differential miRNA expression to various stress responses, including the anoxia response in adaptive invertebrates (Hadj-Moussa et al, 2018;Biggar et al, 2012;Lyons et al, 2015;Morin et al, 2008). In this study, 76 miRNAs were examined, and their potential involvement in coordinating the unique suite of adaptations required to survive and overcome anoxia-associated challenges was investigated.…”

“…Under such conditions, these processes have been found to be differentially regulated in a tissue-specific manner in response to the unique metabolic requirements of each organ (Ziello et al, 2007). For instance, anoxia-induced responses have been shown to be tissue specific in various other models of hypoxia and anoxia tolerance, such as turtles, frogs and squid (Mattice et al, 2018;Al-attar et al, 2017;Gerber et al, 2016;Hadj-Moussa et al, 2018;Krivoruchko and Storey, 2015).…”

microRNA profiling in the Weddell seal suggests novel regulatory mechanisms contributing to diving adaptation

“…These small non-coding RNAs also regulate seasonal phenotypic shifts, including metabolic depression that accompanies hibernation, anoxia tolerance and estivation in several vertebrates, although the exact miRNAs that may regulate these transitions appear speciesspecific [21,22]. MiRNAs are also implicated in protection against environmental stresses such as hypoxia, extreme temperature and nutrient limitation in animals and plants [23][24][25].…”

Estivation-responsive microRNAs in a hypometabolic terrestrial snail

“…MiRNA-mediated regulation of gene expression has been well established as part of a typical stress response (e.g., during ischemic injury, cardiac hypertrophy, etc.) and recent studies have highlighted their role in multiple forms of environmental stress-induced hypometabolism (Biggar & Storey, 2018) including mammalian hibernation (Hadj-Moussa et al., 2016), hypoxia/anoxia tolerance (Biggar et al., 2012; Hadj-Moussa et al., 2018), estivation (Chen et al., 2013; Wu, Biggar & Storey, 2013; Chen & Storey, 2014; Luu & Storey, 2015), insect cold-hardiness/diapause (Lyons et al., 2015), and freeze tolerance (Biggar et al., 2012; Lyons et al., 2013; Hadj-Moussa & Storey, 2018). These studies linked differential miRNA expression to protective actions in the hypometabolic state including minimizing apoptosis and muscle wasting, limiting non-essential energy-expensive processes, promoting cell cycle arrest, and differentially regulating selected signalling cascades (Biggar & Storey, 2011).…”