Transcriptional landscape of human endogenous retroviruses (HERVs) and other repetitive elements in psoriatic skin

Abstract

Human endogenous retrovirus (HERV) sequences make up at least 8% of the human genome. Transcripts originating from these loci as well as proteins encoded by them have been detected in various tissues. HERVs are believed to be implicated in autoimmune diseases, however the extent to which, has remained unclear. Differential expression studies have so far been limited to certain HERV subfamilies with conserved sequences. No studies have been published describing the genome-wide expression pattern of HERVs and repetitive elements in the context of psoriasis. In the present study, we analysed total RNA sequencing data from skin samples of 12 psoriasis patients and 12 healthy controls, which enabled us to describe the entire transcriptional landscape of repetitive elements. We report high levels of repetitive element expression in the skin of psoriasis patients as well as healthy controls. The majority of differentially expressed elements were downregulated in lesional and non-lesional skin, suggesting active HERV suppression in the pro-inflammatory environment of psoriatic skin. However, we also report upregulation of a small subset of HERVs previously described in the context of autoimmune diseases, such as members of the HERV-K and W families, with the potential to affect the immunopathogenesis of psoriasis.

Peer Review #2 of "Biomarker potential of repetitive-element transcriptome in lung cancer (v0.2)"

“…show minimal differential expression (Supplemental Tables S3 and S6), indicating that RE expression change should not be related to families but particular REs. It further supports the established proposal that RE expression seems to be strictly controlled before and after any oncogenic transformation (Gibb et al, 2015;Clayton et al, 2016;Lättekivi et al, 2018;Arroyo et al, 2018) and cannot be explained by a broad deregulation as initially proposed by Shalgi et al (Shalgi et al, 2010).…”

“…The fact that lung cancers display more down-regulation than up-regulation of HERVs and REs in general coincides with recent transcriptomic studies of REs in psoriatic skin (Lättekivi et al, 2018) and…”

“…by (Criscione et al, 2014), 12.44% using our workflow) and mouse lung cancers (Faulkner et al, 2009), or the 27.5% reported in psoriatic skin (Lättekivi et al, 2018). The underlying cause of the low level of multi-mapping reads in SCLC and LUAD samples might be more likely related to biological (lower RE expression) or methodological (removal of RE sequences during RNA preparation) reasons rather than bioinformatic processing (more stringent read pre-processing, different mapping functions and filtering).…”

“…Manuscript to be reviewed (Sacha et al, 2012). Bioinformatic tools such as RepEnrich (Criscione et al, 2014) have been developed to quantify differential expression of REs, demonstrating, for example, that LINE-1 is up-regulated in prostate cancer cells (Criscione et al, 2014) and HERVs are down-regulated in psoriasis (Lättekivi et al, 2018). Hence, discovery of new lung cancer biomarkers based on RE transcriptome was faced since it is feasible and underdeveloped.…”

“…Regarding differential expression of REs in Figs. 3 and 4, ERVs, particularly the LTR class of HERV elements, are the most affected, as also occurs in psoriatic skin (Lättekivi et al, 2018) and…”