Broecker, Felix, Horton, Roger, Heinrich, Jochen, Franz, Alexandra, Schweiger, Michal-Ruth, Lehrach, Hans and Moelling, Karin (2016). The intron-enriched HERV-K(HML-10) family suppresses apoptosis, an indicator of malignant transformation. Mob. DNA, 7. LONDON: BMC. ISSN 1759-8753

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Abstract

Background: Human endogenous retroviruses (HERVs) constitute 8% of the human genome and contribute substantially to the transcriptome. HERVs have been shown to generate RNAs that modulate host gene expression. However, experimental evidence for an impact of these regulatory transcripts on the cellular phenotype has been lacking. Results: We characterized the previously little described HERV-K(HML-10) endogenous retrovirus family on a genome-wide scale. HML-10 invaded the ancestral genome of Old World monkeys about 35 Million years ago and is enriched within introns of human genes when compared to other HERV families. We show that long terminal repeats (LTRs) of HML-10 exhibit variable promoter activity in human cancer cell lines. One identified HML-10 LTR-primed RNA was in opposite orientation to the pro-apoptotic Death-associated protein 3 (DAP3). In HeLa cells, experimental inactivation of HML-10 LTR-primed transcripts induced DAP3 expression levels, which led to apoptosis. Conclusions: Its enrichment within introns suggests that HML-10 may have been evolutionary co-opted for gene regulation more than other HERV families. We demonstrated such a regulatory activity for an HML-10 RNA that suppressed DAP3-mediated apoptosis in HeLa cells. Since HML-10 RNA appears to be upregulated in various tumor cell lines and primary tumor samples, it may contribute to evasion of apoptosis in malignant cells. However, the overall weak expression of HML-10 transcripts described here raises the question whether our result described for HeLa represent a rare event in cancer. A possible function in other cells or tissues requires further investigation.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Broecker, FelixUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Horton, RogerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heinrich, JochenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franz, AlexandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schweiger, Michal-RuthUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lehrach, HansUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moelling, KarinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-252704
DOI: 10.1186/s13100-016-0081-9
Journal or Publication Title: Mob. DNA
Volume: 7
Date: 2016
Publisher: BMC
Place of Publication: LONDON
ISSN: 1759-8753
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DEATH-ASSOCIATED PROTEIN-3; LONG TERMINAL REPEATS; TRANSCRIPTIONAL ACTIVITY; ENDOGENOUS RETROVIRUSES; ANTISENSE TRANSCRIPTS; PROMOTER ACTIVITY; INTERFERON-GAMMA; IN-VIVO; REGULATORY ROLES; SITE SELECTIONMultiple languages
Genetics & HeredityMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/25270

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