Generalized nuclear localization of retroelement transcripts

Abstract

Background LINE-1s, Alus and SVAs are the only retrotransposition competent elements in humans. Their mobilization followed by insertional mutagenesis is often linked to disease. Apart from these rare integration events, accumulation of retrotransposition intermediates in the cytoplasm is potentially pathogenic due to induction of inflammatory response pathways. Although the retrotransposition of LINE-1 and Alu retroelements has been studied in considerable detail, there are mixed observations about the localization of their RNAs. Results We undertook a comprehensive and unbiased approach to analyze retroelement RNA localization using common cell lines and publicly available datasets containing RNA-sequencing data from subcellular fractions. Using our customized analytic pipeline, we compared localization patterns of RNAs transcribed from retroelements and single-copy protein coding genes. Our results demonstrate a generalized characteristic pattern of retroelement RNA nuclear localization that is conserved across retroelement classes as well as evolutionarily young and ancient elements. Preferential nuclear enrichment of retroelement transcripts was consistently observed in cell lines, in vivo and across species. Moreover, retroelement RNA localization patterns were dynamic and subject to change during development, as seen in zebrafish embryos. Conclusion The pronounced nuclear localization of transcripts arising from ancient as well as de novo transcribed retroelements suggests that these transcripts are retained in the nucleus as opposed to being re-imported to the nucleus or degraded in the cytoplasm. This raises the possibility that there is adaptive value associated with this localization pattern to the host, the retroelements or possibly both.

State‐of‐the‐art in transposable element modulation affected by drugs in malignant prostatic cancer cells

“…Some studies have highlighted possible interactions with antioncogenes, such as TP53 in cancer cells, in which its deletion is closely linked to progression and increase in L1 expression. 7,31,42,56 A correlation between p53 and L1 inhibition has been demonstrated in normal and cancerous lung cells. On one hand, the binding of p53 to 5′UTR of L1 prevents its expression and enhances repressive histone mark depositions in L1 promoter.…”

“…Therefore, the analysis of RNAi component levels could be a valuable internal biomarker for assessing potential TE reactivation. 31,37,43 The key mechanisms involved in the regulation of repetitive elements in cancer are reported in Table 1.…”

“…7,58,59 The increased presence of L1 transcripts in nuclei appears to be a protective mechanism that TEs have developed to escape these cytoplasmic defenses. 31 SINEs seemingly hinder gene expression, limiting their presence near transcriptionally active regions, except when protected by insulators. Consequently, active SINEs can silence susceptible promoters, leading to epigenetic reprogramming.…”

“…7 Das et al highlight the potential "ferryman" role of certain TEs, with specific sequences such as LINE2b, MIRb, and MIRc interacting with long noncoding RNAs in the nucleus, mediating mobility and transport across the genome. 31,60 Furthermore, TEs are also known to modulate the immune system by regulating several transcripts, activating numerous inflammatory pathways, and affecting cellular components through the formation of hybrid TEs/RNA and DNA structures. Among mobile elements, HERV modulates innate immunity.…”

“…Among mobile elements, HERV modulates innate immunity. 9,31,61 Additionally, HERVK, typically silenced, can be reactivated under specific conditions, playing a critical role during viral infections. This aspect may be relevant in inflammationmediated pathologies, such as cancer, in which increased HERV transcript levels have also been observed.…”