Transposable elements as essential elements in the control of gene expression

Abstract

Interspersed repetitions called transposable elements (TEs), commonly referred to as mobile elements, make up a significant portion of the genomes of higher animals. TEs contribute in controlling the expression of genes locally and even far away at the transcriptional and post-transcriptional levels, which is one of their significant functional effects on gene function and genome evolution. There are different mechanisms through which TEs control the expression of genes. First, TEs offer cis-regulatory regions in the genome with their inherent regulatory features for their own expression, making them potential factors for controlling the expression of the host genes. Promoter and enhancer elements contain cis-regulatory sites generated from TE, which function as binding sites for a variety of trans-acting factors. Second, a significant portion of miRNAs and long non-coding RNAs (lncRNAs) have been shown to have TEs that encode for regulatory RNAs, revealing the TE origin of these RNAs. Furthermore, it was shown that TE sequences are essential for these RNAs' regulatory actions, which include binding to the target mRNA. By being a member of cis-regulatory and regulatory RNA sequences, TEs therefore play essential regulatory roles. Additionally, it has been suggested that TE-derived regulatory RNAs and cis-regulatory regions both contribute to the evolutionary novelty of gene regulation. Additionally, these regulatory systems arising from TE frequently have tissue-specific functions. The objective of this review is to discuss TE-mediated gene regulation, with a particular emphasis on the processes, contributions of various TE types, differential roles of various tissue types, based mostly on recent studies on humans.

Keywords: Gene expression; Mobile elements; Transposable elements.

Fig. 1

TEs are regulated in both healthy and cancerous cells. Epigenetic changes such as DNA methylation, histone modification, and non-coding RNA (eg cirRNA, miRNA, and lncRNA) inhibit the function of TEs in healthy cells (left panel). During cellular transformation, hypomethylation with increased S-Adenosyl methionine (SAM), various histone modifications (like methylation and acetylation), and oncogenic non-coding RNAs, which inhibit the expression of tumor suppressor genes (TSGs), all contribute to the loss of repressive signals and the uncontrolled production of TEs in cancer cells (right panel). DNA breakdown, mutations, and genomic instability result from all these (arrows indicate the increased activity, cross circle indicates inhibition; ( +) sign indicates increment, (–) sign indicates decrement, and cross sign indicates inhibition) [26]

Fig. 2

Different mechanisms that TEs influence gene expression regulation

Fig. 3

The consequence of TE distribution on the epigenetic control of gene expression due to changes in methylation of histones and DNA across species, tissues of the same organisms, and stimuli or circumstances. A The epigenetic control of a particular gene is altered by the varied distribution of TEs in evolution. TE element controls gene expression by influencing the local chromatin state due to changes in methylation of histones and DNA. B The expression of a particular gene is impacted by the differential redistribution of TEs in various cells and tissues of the same organism during development. C The expression of a certain gene is influenced by the relocalization of TEs sequence in the same cell following a particular stimulus or circumstance

Fig. 4

Regulation of gene expression by TE-dependent post-transcription. A The presence of an upstream ORF that contributes in the control of the main ORF translation is brought about by a TE inside the 5'-UTR; B The existence of an extra domain inside the encoded protein is determined by the exonization of a TE and consequently its translation; C The presence of a premature stop codon due to the exonization of a TE inside the coding region of an mRNA can lead to the Nonsense-mediated Decay process; D The alternative splicing process can be impacted by TE sequence interactions with RNA-binding proteins (RBP); E An mRNA's 3'-UTR contains TE sequences that might cause STAU-mediated degradation; F acts as a docking point for RBP important in maintaining RNA stability, such as the HuR protein; G or causes the production of a shorter, poly-A tailless mRNA, which results in translational repression