Human Endogenous Retrovirus K (HERV-K) can drive gene expression as a promoter in Caenorhabditis elegans

Abstract

Endogenous retroviruses (ERVs) are retrotransposons present in various metazoan genomes and have been implicated in metazoan evolution as well as in nematodes and humans. The long terminal repeat (LTR) retrotransposons contain several regulatory sequences including promoters and enhancers that regulate endogenous gene expression and thereby control organismal development and response to environmental change. ERVs including the LTR retrotransposons constitute 8% of the human genome and less than 0.6% of the Caenorhabditis elegans ( C. elegans ) genome, a nematode genetic model system. To investigate the evolutionarily conserved mechanism behind the transcriptional activity of retrotransposons, we generated a transgenic worm model driving green fluorescent protein (GFP) expression using Human endogenous retroviruses (HERV)-K LTR as a promoter. The promoter activity of HERV-K LTR was robust and fluorescence was observed in various tissues throughout the developmental process. Interestingly, persistent GFP expression was specifically detected in the adult vulva muscle. Using deletion constructs, we found that the region from positions 675 to 868 containing the TATA box was necessary for promoter activity driving gene expression in the vulva. Interestingly, we found that the promoter activity of the LTR was dependent on che-1 transcription factor, a sensory neuron driver, and lin-15b , a negative regulator of RNAi and germline gene expression. These results suggest evolutionary conservation of the LTR retrotransposon activity in transcriptional regulation as well as the possibility of che-1 function in non-neuronal tissues.

Human Endogenous Retroviruses: Friends and Foes in Urology Clinics

“…• HERV1: Homologous recombination • Disrupting EYA1 gene in rats [55] • HERV signatures associated with ccRCC prognosis [52] Uterus (female) • SYN-1, SYN-2, SUPYN in placenta [2,3,11,132,133] • HERVs in endometria and pregnancy [135][136][137][138][139][140][141] Prostate (male) • HERV-K (HML-2) [33] • HERV transcription profiles [38][39][40][41] • Irradiation [35] and Arsenic [36] • RT inhibitors [37] • RNase L and OAS [13] Fig. 1.…”

“…HERVs are actively transcribed in various cancers, including prostate cancer [ 2 , 3 ]. HERV-K (HML-2) transcripts are detected in prostate cell lines such as LNCaP, DU145, PC3, and VCaP [ 33 ].…”

“…Human endogenous retroviruses (HERVs) have infected and integrated into the human germline, mostly after the divergence of the New and the Old World monkeys [1][2][3][4]. Over millions of years, the human genome has accumulated hundreds of thousands of HERVs and related retrotransposons, comprising approximately 8% of the human genome [5,6].…”

Human Endogenous Retroviruses as Gene Expression Regulators: Insights from Animal Models into Human Diseases

“…Promoter activity of HERV-K LTR that is assessed by expressing GFP is reported in free-living soil worms C. elegans ( Durnaoglu et al, 2020 ). Expression of GFP is mainly observed in vulval muscle, and LTR activation is dependent on che-1 , a sensory neuron driver, and lin-15b , a negative regulator of RNAi and germline gene expression.…”

“…LTR-overlapping transcripts specific in certain cancers raises the possibility that the highly predictable transcripts can provide disease prognosis and information of cancer-specific antigenicity ( Attig et al, 2019 ). Recently, the infectious disease COVID-19 has been reported to modulate the expression of some HERV genes, and HERV promoter activities are retained in some non-human animal models ( Balestrieri et al, 2021 ; Casau et al, 1999 ; Durnaoglu et al, 2020 ; Garcia-Montojo and Nath, 2021 ; Levet et al, 2017 ; Pi et al, 2004 ; Tanaka et al, 2003 ; Tovo et al, 2021 ). In this review, we summarize various modes of HERV activation and their interacting molecular components and regulatory signaling networks.…”