Abstract
Transposable elements (TEs), also known as mobile elements (MEs), are interspersed repeats that constitute a major fraction of the genomes of higher organisms. As one of their important functional impacts on gene function and genome evolution, TEs participate in regulating the expression of genes nearby and even far away at transcriptional and post-transcriptional levels. There are two known principal ways by which TEs regulate the expression of genes. First, TEs provide cis-regulatory sequences in the genome with their intrinsic regulatory properties for their own expression, making them potential factors for regulating the expression of the host genes. TE-derived cis-regulatory sites are found in promoter and enhancer elements, providing binding sites for a wide range of trans-acting factors. Second, TEs encode for regulatory RNAs with their sequences showed to be present in a substantial fraction of miRNAs and long non-coding RNAs (lncRNAs), indicating the TE origin of these RNAs. Furthermore, TEs sequences were found to be critical for regulatory functions of these RNAs, including binding to the target mRNA. TEs thus provide crucial regulatory roles by being part of cis-regulatory and regulatory RNA sequences. Moreover, both TE-derived cis-regulatory sequences and TE-derived regulatory RNAs have been implicated in providing evolutionary novelty to gene regulation. These TE-derived regulatory mechanisms also tend to function in a tissue-specific fashion. In this review, we aim to comprehensively cover the studies regarding these two aspects of TE-mediated gene regulation, mainly focusing on the mechanisms, contribution of different types of TEs, differential roles among tissue types, and lineage-specificity, based on data mostly in humans.
Highlights
Transposable elements (TEs), known as mobile elements (MEs), are interspersed repeats that constitute a major fraction of the genomes of higher organisms
In addition to their regular internal promoters, some TEs, such as L1s, contain active antisense promoters (ASP), which can drive the generation of additional antisense transcripts that usually extend into the neighboring regions to form chimeric transcripts of known genes as a mechanism to interfere normal gene expression [54]
In a recent work by Zeng et al [67], TE enrichment was determined in different regulatory regions by measuring “P(TE|RE)”, the probability of nucleotide in the regulatory element being from the TE
Summary
Transposable elements (TEs), known as mobile elements (MEs), are interspersed repeats constituting a major fraction of the genomes in higher organisms. As will be discussed in this review, the two principal methods by which TEs regulate the expression of genes are the function as cis-acting regulatory sequences and encoding of regulatory RNAs. Ongoing TE insertions of certain TE subfamilies in the human genome can lead to insertions of TEs in genic regions and alteration in the level of gene expression via different mechanisms, including alternative splicing, the introduction of a premature stop codon, and introduction of polyadenylation and termination signals, etc. Ongoing TE insertions of certain TE subfamilies in the human genome can lead to insertions of TEs in genic regions and alteration in the level of gene expression via different mechanisms, including alternative splicing, the introduction of a premature stop codon, and introduction of polyadenylation and termination signals, etc. TE-mediated gene regulation tend to be tissue-specific? Does TE-mediated gene regulation lead to evolutionary novelty? (3) How different classes of TEs differ in contributing to gene regulation?
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