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 2 h anoxia, and chronic 20 h anoxia exposures. MicroRNAs are known to regulate a diverse array of cellular functions required for environmental stress adaptations, and here we explored their role in anoxia tolerance. The tissue-specific anoxia responses observed herein, with 22 anoxia-responsive microRNAs in the hepatopancreas and only four 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 liverlike 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 the 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 oxygenpoor environments is critical to elucidating the vast and substantial role of microRNAs in the regulation of metabolism and stress in aquatic invertebrates.

Naked mole rats activate neuroprotective proteins during hypoxia

“…An interesting NMR‐specific adaptation reported by Xiao et al () was that HIF1α was expressed at a higher level in NMR brains as compared to mouse brains, possibly contributing to their elevated hypoxia tolerance and likely due to their unique HIF1α protein sequence (Xiao et al, ). This activation of HIF1α has also been observed in other animal models of metabolic rate depression and anoxia/hypoxia tolerance, an observation that has been made at the protein, mRNA, and noncoding RNA levels (English, Hadj‐Moussa, & Storey, ; Gorr, ; Maistrovski, Biggar, & Storey, ; Morin, McMullen, & Storey, ).…”

Structural Adaptation of a Protein to Increased Metal Stress: NMR Structure of a Marine Snail Metallothionein with an Additional Domain

“…The biological role of MTs varies in a cell‐ and species‐specific manner, but in most cases, they contribute to d‐block metal regulation and detoxification. Interestingly, MTs seem also to be involved in metal metabolism and stress resistance in gastropods, as shown for the terrestrial snail Helix pomatia and the marine common periwinkle Littorina littorea . The Littorina littorea MT gene has been shown to be strongly up‐regulated in response to stressors .…”

“…Interestingly, MTs seem also to be involved in metal metabolism and stress resistance in gastropods, as shown for the terrestrial snail Helix pomatia and the marine common periwinkle Littorina littorea . The Littorina littorea MT gene has been shown to be strongly up‐regulated in response to stressors . Moreover, it has been shown that Littorina littorea accumulates Cd 2+ in different tissues and subcellular structures …”

Strukturanpassung eines Proteins an Metallbelastung: NMR‐Struktur eines marinen Schnecken‐Metallothioneins mit einer zusätzlichen Domäne

“…Die biologische Funktion der MTs variiert in zell‐ und artspezifischer Weise, ist jedoch in den meisten Fällen auf die Regulation und Entgiftung von d‐Block‐Metallen ausgerichtet. MTs von Gastropoden scheinen jedenfalls in den Metallstoffwechsel und in die Stressresistenz involviert zu sein, wie dies etwa für die terrestrische Schnecke Helix pomatia und die marine Strandschnecke Littorina littorea gezeigt werden konnte . Für das MT‐Gen von Littorina littorea konnte eine starke Hochregulierung als Antwort auf Stressfaktoren nachgewiesen werden .…”

“…MTs von Gastropoden scheinen jedenfalls in den Metallstoffwechsel und in die Stressresistenz involviert zu sein, wie dies etwa für die terrestrische Schnecke Helix pomatia und die marine Strandschnecke Littorina littorea gezeigt werden konnte . Für das MT‐Gen von Littorina littorea konnte eine starke Hochregulierung als Antwort auf Stressfaktoren nachgewiesen werden . Zudem wurde gezeigt, dass Littorina littorea in verschiedenen Geweben und subzellulären Strukturen Cd 2+ akkumuliert …”