GSE158831
Organ-, sex-, and age-dependent patterns of endogenous LINE-1 mRNA expression at a single locus resolution
Expression of full-length LINE-1 mRNA, the first step in the L1 copy-and-paste amplification cycle, is a prerequisite for L1-associated genomic instability resulting from DNA damage and insertional mutagenesis. We used our stringent bioinformatics method to parse L1 mRNA transcripts and measure the level of full-length L1 mRNA expressed in mouse and rat organs at a locus-specific resolution. We find that expression of L1 loci in rodents exhibits striking organ specificity with less than 0.8% of loci shared between different organs of the same organism. This organ specificity in L1 mRNA expression is preserved in male and female mice and across different age groups. Unexpectedly, we discovered notable differences in L1 mRNA expression between sexes with only 5% of expressed L1 loci shared between male and female mice. Moreover, we report that the levels of total L1 mRNA expression and the number and spectrum of expressed L1 loci fluctuate with age as independent variables, demonstrating different patterns in different organs and sexes. Overall, our comparisons between organs and sexes and across ages ranging from 2 to 22 months establish previously unforeseen dynamic changes in L1 mRNA expression in vivo. These milestone findings establish a previously lacking atlas of endogenous L1 mRNA expression across a broad range of biological variables that will guide future studies addressing the understanding of mechanisms that govern expression of a limited number of L1 loci in any given organ and the impact of environmental and genetic perturbations on L1 mRNA expression and its involvement in disease initiation and progression. Overall design: RNA Sequencing of multiple organs from 12 male mice, 9 female mice, and 3 rats. Mouse samples are from ages ranging 2-22 months. Testes, brains, and livers were collected from 6 mice: 3 at 7.6 months old (mo) and 3 at 12.8 mo. Lungs were collected from 5 mice: 2 at 7.6 mo and 3 at 12.8 mo. Only testes and livers were collected from 6 additional mice: 2 at 1.9 mo, 1 at 3.6 mo, and 3 at 22.3 mo. Brains, lungs, and ovaries were collected from 9 mice: 2 at 2.2 mo, 1 at 3.2 mo, 2 at 8 mo, 1 at 8.6 mo, 1 at 8.7 mo, and 2 at 16.5 mo. Uteri were collected from 6 mice: 1 at 2.2 mo, 1 at 8 mo, 1 at 8.6 mo, 1 at 8.7 mo, and 2 at 16.5- mo Testes, brains, livers, and lungs were collected from 3 rats, all 4.8 mo. The .fastq files contain RNA-sequencing of the whole cytoplasm. The .txt files contain analysis of the LINE-1 retrotransposon which has ~3,000 full length copies scattered throughout the mouse genome.