The highs and lows of ionizing radiation and its effects on protein synthesis

Abstract

Ionizing radiation (IR) is a constant feature of our environment and one that can dramatically affect organismal health and development. Although the impacts of high-doses of IR on mammalian cells and systems have been broadly explored, there are still challenges in accurately quantifying biological responses to IR, especially in the low-dose range to which most individuals are exposed in their lifetime. The resulting uncertainty has led to the entrenchment of conservative radioprotection policies around the world. Thus, uncovering long-sought molecular mechanisms and tissue responses that are targeted by IR could lead to more informed policymaking and propose new therapeutic avenues for a variety of pathologies. One often overlooked target of IR is mRNA translation, a highly regulated cellular process that consumes more than 40% of the cell's energy. In response to environmental stimuli, regulation of mRNA translation allows for precise and rapid changes to the cellular proteome, and unsurprisingly high-dose of IR was shown to trigger a severe reprogramming of global protein synthesis allowing the cell to conserve energy by preventing the synthesis of unneeded proteins. Nonetheless, under these conditions, certain mRNAs encoding specific proteins are translationally favoured to produce the factors essential to repair the cell or send it down the path of no return through programmed cell death. Understanding the mechanisms controlling protein synthesis in response to varying doses of IR could provide novel insights into how this stress-mediated cellular adaptation is regulated and potentially uncover novel targets for radiosensitization or radioprotection. Here, we review the current literature on the effects of IR at both high- and low-dose on the mRNA translation machinery.

Keywords: High and low-dose radiation; Ionizing radiation; Ribosome; Translation control; Translation initiation factors; mRNA translation.