Dataset Information

Human endogenous retrovirus K homologous sequences and their coding capacity in Old World primates.

ABSTRACT: The coding capacity for retroviral Gag and Env proteins has been maintained in human endogenous retroviruses of the HERV-K family. HERV-K homologous sequences have been found in all Old World primates. Here, we examined Old World primate species for the presence of full-length HERV-K gag and env genes and the presence of gag and env open reading frames as determined by the protein truncation test. Full-length HERV-K env genes were found in DNAs of all Old World primate species, whereas open reading frames for Env protein were found solely in human, chimpanzee, and gorilla DNAs. The mutational event leading to two HERV-K types was found to have occurred after the separation of hominids from lower Old World primates and before the expansion of hominids. Full-length HERV-K gag genes in hominids displayed a 96-bp deletion compared to those in lower Old World primates. The ancient gag variant has not been maintained during hominid evolution. Open reading frames for HERV-K Gag have been found in all Old World primates except chimpanzees. Our study of the HERV-K family during Old World primate evolution contributes to the understanding of their possible biological functions in the host genomes.

SUBMITTER: Mayer J

PROVIDER: S-EPMC109477 | biostudies-literature | 1998 Mar

REPOSITORIES: biostudies-literature

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Human endogenous retrovirus K homologous sequences and their coding capacity in Old World primates.

Mayer J J Meese E E Mueller-Lantzsch N N

Journal of virology 19980301 3

The coding capacity for retroviral Gag and Env proteins has been maintained in human endogenous retroviruses of the HERV-K family. HERV-K homologous sequences have been found in all Old World primates. Here, we examined Old World primate species for the presence of full-length HERV-K gag and env genes and the presence of gag and env open reading frames as determined by the protein truncation test. Full-length HERV-K env genes were found in DNAs of all Old World primate species, whereas open read ...[more]

PMID: 9499038

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Project description:BACKGROUND: Long non-coding RNAs (lncRNAs) are emerging as molecules that significantly impact many cellular processes and have been associated with almost every human cancer. Compared to protein-coding genes, lncRNA genes are often associated with transposable elements, particularly with endogenous retroviral elements (ERVs). ERVs can have potentially deleterious effects on genome structure and function, so these elements are typically silenced in normal somatic tissues, albeit with varying efficiency. The aberrant regulation of ERVs associated with lncRNAs (ERV-lncRNAs), coupled with the diverse range of lncRNA functions, creates significant potential for ERV-lncRNAs to impact cancer biology. METHODS: We used RNA-seq analysis to identify and profile the expression of a novel lncRNA in six large cohorts, including over 7,500 samples from The Cancer Genome Atlas (TCGA). RESULTS: We identified the tumor-specific expression of a novel lncRNA that we have named Endogenous retroViral-associated ADenocarcinoma RNA or 'EVADR', by analyzing RNA-seq data derived from colorectal tumors and matched normal control tissues. Subsequent analysis of TCGA RNA-seq data revealed the striking association of EVADR with adenocarcinomas, which are tumors of glandular origin. Moderate to high levels of EVADR were detected in 25 to 53% of colon, rectal, lung, pancreas and stomach adenocarcinomas (mean?=?30 to 144 FPKM), and EVADR expression correlated with decreased patient survival (Cox regression; hazard ratio?=?1.47, 95% confidence interval?=?1.06 to 2.04, P?=?0.02). In tumor sites of non-glandular origin, EVADR expression was detectable at only very low levels and in less than 10% of patients. For EVADR, a MER48 ERV element provides an active promoter to drive its transcription. Genome-wide, MER48 insertions are associated with nine lncRNAs, but none of the MER48-associated lncRNAs other than EVADR were consistently expressed in adenocarcinomas, demonstrating the specific activation of EVADR. The sequence and structure of the EVADR locus is highly conserved among Old World monkeys and apes but not New World monkeys or prosimians, where the MER48 insertion is absent. Conservation of the EVADR locus suggests a functional role for this novel lncRNA in humans and our closest primate relatives. CONCLUSIONS: Our results describe the specific activation of a highly conserved ERV-lncRNA in numerous cancers of glandular origin, a finding with diagnostic, prognostic and therapeutic implications.

Dataset Information

Human endogenous retrovirus K homologous sequences and their coding capacity in Old World primates.

Publications

Human endogenous retrovirus K homologous sequences and their coding capacity in Old World primates.

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