Locus-specific analysis of Transposable Elements during the progression of ALS in the SOD1G93A mouse model

Abstract

Transposable Elements (TEs) are ubiquitous genetic elements with the ability to move within a genome. TEs contribute to a large fraction of the repetitive elements of a genome, and because of their nature, they are not routinely analyzed in RNA-Seq gene expression studies. Amyotrophic Lateral Sclerosis (ALS) is a lethal neurodegenerative disease, and a well-accepted model for its study is the mouse harboring the human SOD1G93A mutant. In this model, landmark stages of the disease can be recapitulated at specific time points, making possible to understand changes in gene expression across time. While there are several works reporting TE activity in ALS models, they have not explored their activity through the disease progression. Moreover, they have done it at the expense of losing their locus of expression. Depending on their genomic location, TEs can regulate genes in cis and in trans, making locus-specific analysis of TEs of importance in order to understand their role in modulating gene expression. Particularly, the locus-specific role of TEs in ALS has not been fully elucidated. In this work, we analyzed publicly available RNA-Seq datasets of the SOD1G93A mouse model, to understand the locus-specific role of TEs. We show that TEs become up-regulated at the early stages of the disease, and via statistical associations, we speculate that they can regulate several genes, which in turn might be contributing to the genetic dysfunction observed in ALS.

Activation of Transposable Elements in Human Skeletal Muscle Fibers upon Statin Treatment

“…In turn, these mRNAs can have important regulatory roles, such as HPAT5, an Alu-bearing long intergenic noncoding RNA (lincRNA), which regulates primates' early embryonic events [24]. Other examples of TE expression associated with gene expression have been reported in mammalian development [25] and some neurodegenerative diseases [13,26]. Different types of stresses can also modify TE expression.…”

The spatial and cellular portrait of Transposable Element expression during Gastric Cancer

“…Although most TEs are now genetically fixed, they can still become transcriptionally active, which can impact gene regulation 25 . Current evidence supports their role as regulatory elements in health and disease [26][27][28] . In particular, there are many examples of their global derepression and subsequent activation in a wide array of cancer types (reviewed in 29 ).…”

Transposable Elements are differentially activated in cell lineages during the developing murine submandibular gland

“…Although in all cases except P1, the proportion of these TEs is relatively low, I still highlight this result, due to its relevance to identify neighboring genes to those TEs, whose expression might be modulated by them. In turn, each of the locus-specific TE markers was associated to their closest gene, in order to predict their regulatory impact at the pathway level (Figure 8), following a similar approach to that of previous works (12,15,25,26). Most TE-related genes did not have an associated pathway, making it difficult to identify their potential consequences (Supplementary Table 2).…”