Exploring mRNA Translation Strategies for Hypoxia Adaptation Across Distantly Related Metazoans

Abstract

Adaptation to variations in oxygen concentration is a conserved mechanism in all metazoans. Extensive studies have been focused on the roles of hypoxia-inducible factors (HIFs) in response to hypoxia. However, HIF1α is not conserved in all animals, and HIF2α and HIF3α are only observed in vertebrates. In this review, we discuss mechanisms enabling three cross-species to adapt to hypoxic conditions. Using transcriptomic data of hypoxia-induced genes from distantly related metazoans, we analyzed the enrichment and conservation of mRNA determinants such as transcript, CDS, 5′UTR and 3′UTR size. We found that long genes are enriched in hypoxia-induced transcripts and might be translated in a 3′UTR-dependent manner. We hope our work can provide a new direction on investigating alternative mechanisms for mRNA translation under hypoxia.

Plain language summary

Many studies have focused on a group of proteins called hypoxia-inducible factors (HIFs) that help animals adapt to different oxygen concentrations, but not all animals have the same HIF proteins. This means that some genes involved in oxygen adaptation work differently in different animals. In this review, we look at three different species and how they adapt to low oxygen levels, with a special focus on how genes are used to make proteins. We used information from these species to see if certain features of genes (like their size) are important for adaptation. We found that in response to low oxygen, longer genes become more active and may use a specific part of the gene to make proteins. However, some common features thought to be important for gene activity in low oxygen were not found to be significant. This research gives us new directions to explore how genes make proteins in low-oxygen conditions, which is important for understanding how animals survive in changing environments.

Keywords::

• 3′UTR
• HIF
• hypoxia
• invertebrates
• mechanism
• translation

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2023-0245

Acknowledgments

The authors thank Felipe S Barreto for providing original data for Tigriopus californicus.

Financial disclosure

This work was supported by the China Scholarship Council (no. 201509110144 to M Liang, 201807650002 to Q Zhao), Shandong Province Science Foundation for Youths (no. ZR2022QC216), the National Natural Science Foundation of China (no. 22207077). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.