Scatter Irradiation of Rat Brain Triggers Sex- and Brain Region-Specific Changes in the Expression of Non-Coding RNA Fragments

Abstract

Non-coding RNA fragments (ncRFs) are small RNA fragments processed from non-coding RNAs (ncRNAs). ncRFs have various functions and are commonly tissue-specific, and their processing is altered by exposure to stress. Information about ncRFs in the brain is scarce. Recently, we reported the brain region-specific and sex-specific expression of ncRNAs and their processing into ncRFs. Here, we analyzed the expression of ncRFs in the frontal cortex (FC), hippocampus (HIP), and cerebellum (CER) of male and female rats exposed to scatter radiation. We found multiple brain region- and sex-specific changes in response to scatter radiation. Specifically, we observed decreased miRNA expression and the increased expression of ra-ncRNA reads in HIP and CER, as well as an increased number of mtR-NA-associated reads in HIP. We also observed the appearance of sense-intronic ncRNAs—in females, in HIP and FC, and in males, in CER. In this work, we also show that tRNA-GlyGCC and tRNA-GlyCCC are most frequently processed to tRFs, in CER in females, as compared to males. An analysis of the targeted pathways revealed that tRFs and snoRFs in scatter radiation samples mapped to genes in several pathways associated with various neuronal functions. While in HIP and CER these pathways were underrepresented, in FC, they were overrepresented. Such changes may play an important role in pathologies that develop in response to scatter radiation, the effect known as “radio-brain”, and may in part explain the sex-specific differences observed in animals and humans exposed to radiation and scatter radiation.

Systemic Genome Correlation Loss as a Central Characteristic of Spaceflight

“…This gene is particularly responsible for the conversion of uridine to pseudouridine at specific ribosomal or small nuclear RNA residues (9). SNORA81 is known to be enriched in neurodegenerative diseases such as Parkinson’s disease (10) and in stroke incidents (11). Additionally, SNORA81 was recently identified as an important factor in RNA deregulation in Amyotrophic Lateral Sclerosis (12), a rare neuromuscular disease characterized by the progressive degeneration of motor neurons in the spinal cord, brainstem, and motor cortex (13).…”

Systemic Genome Correlation Loss as a Central Characteristic of Spaceflight

“…This gene is particularly responsible for the conversion of uridine to pseudouridine at specific ribosomal or small nuclear RNA residues (9). SNORA81 is known to be enriched in neurodegenerative diseases such as Parkinson's disease (10) and in stroke incidents (11). Additionally, SNORA81 was recently identified as an important factor in RNA deregulation in Amyotrophic Lateral Sclerosis (12), a rare neuromuscular disease characterized by the progressive degeneration of motor neurons in the spinal cord, brainstem, and motor cortex (13).…”