Abstract
BackgroundRetrotransposons are mobile elements that have a high impact on shaping the mammalian genomes. Since the availability of whole genomes, genomic analyses have provided novel insights into retrotransposon biology. However, many retrotransposon families and their possible genomic impact have not yet been analysed.ResultsHere, we analysed the structural features, the genomic distribution and the evolutionary history of mouse VL30 LTR-retrotransposons. In total, we identified 372 VL30 sequences categorized as 86 full-length and 49 truncated copies as well as 237 solo LTRs, with non-random chromosomal distribution. Full-length VL30s were highly conserved elements with intact retroviral replication signals, but with no protein-coding capacity. Analysis of LTRs revealed a high number of common transcription factor binding sites, possibly explaining the known inducible and tissue-specific expression of individual elements. The overwhelming majority of full-length and truncated elements (82/86 and 40/49, respectively) contained one or two specific motifs required for binding of the VL30 RNA to the poly-pyrimidine tract-binding protein-associated splicing factor (PSF). Phylogenetic analysis revealed three VL30 groups with the oldest emerging ~17.5 Myrs ago, while the other two were characterized mostly by new genomic integrations. Most VL30 sequences were found integrated either near, adjacent or inside transcription start sites, or into introns or at the 3′ end of genes. In addition, a significant number of VL30s were found near Krueppel-associated box (KRAB) genes functioning as potent transcriptional repressors.ConclusionCollectively, our study provides data on VL30s related to their: (a) number and structural features involved in their transcription that play a role in steroidogenesis and oncogenesis; (b) evolutionary history and potential for retrotransposition; and (c) unique genomic distribution and impact on gene expression.Electronic supplementary materialThe online version of this article (doi:10.1186/s13100-016-0066-8) contains supplementary material, which is available to authorized users.
Highlights
Retrotransposons are mobile elements that have a high impact on shaping the mammalian genomes
We found that the number of transcription factors (TFs) binding sites (TFBS) largely varied depending on the particular Viral-like 30 elements (VL30s) Long Terminal Repeat (LTR), we identified 10,371 transcription factor binding sites (TFBS) allocated to 53 distinct TFs, common to 70 % of 86 new full-length elements, and a total number of 14,880 TFBS from 197 TFs in all 5′ LTRs analyzed (Additional file 2)
VL30s contain a large repertoire of TFBS (Additional file 2) and are competent of inducible [5, 8] and cell type-specific expression [6]; and (iii) Mouse VL30s inserted near genes affect their expression [14]; we suggest that the unique genomic distribution of VL30s near genes, such as those of the Krueppel-associated box (KRAB) gene family, might lead to their selection as functional elements influencing epigenetic gene regulation and participating in regulatory networks
Summary
Retrotransposons are mobile elements that have a high impact on shaping the mammalian genomes. Viral-like 30 elements (VL30s) are a family of 5–6 Kb retrovirus-like DNA sequences present in mouse and rat genomes, and are classified as LTR retrotransposons [4]. VL30s are considered as immediate early response genes as their RNA expression is rapidly induced following transient inhibition of protein synthesis or mitogenic stimulation [10, 11]. Another important feature of VL30s is that their RNA is packaged into C-type retroviral particles of murine leukemia viruses and can be transmitted to heterologous cells [12, 13], making them an important potential tool for gene transfer. Induced VL30 RNA seems to be a critical factor involved in oncogenesis and steroidogenesis [15, 16], as it contains specific motifs for binding to spliceosome factor (PSF), leading to RNA induction of PSF-repressed genes
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