4 research outputs found
HERV-K-T47D-Related Long Terminal Repeats Mediate Polyadenylation of Cellular Transcripts.
The human genome harbors thousands of long terminal repeats (LTRs) that are derived from endogenous retroviruses and contain elements able to regulate the expression of neighboring cellular genes. We have investigated the ability of human endogenous retroviral (HERV)-K LTRs to provide transcriptional processing signals for nonviral sequences. Four chimeric cDNA clones isolated from a cDNA library derived from the human cell line T47D were found to be polyadenylated within an HERV-K-T47D-related LTR. Two transcripts containing an as yet unknown cellular sequence were probably derived from the same genomic locus but their 3' ends were processed at different positions of the LTR. Structural analysis of the polyadenylation site suggests RNA stem-loop structures similar to the HTLV-1 Rex responsive element that bring the two remote AAUAAA and GU-rich elements into the spatial juxtaposition necessary for correct 3' end processing. The cellular part of the third chimeric clone shows significant homology to an exon of the human tyrosine phosphatase 1 gene, although oriented in the antisense direction compared to the adjacent LTR. Furthermore, we found that the 3' untranslated region of the human transmembrane tyrosine kinase gene FLT4 is probably derived from a partial HERV-K-T47D LTR sequence. Taken together, our data suggest that LTRs of the HERV-K-T47D family display biological function by mediating polyadenylation of cellular sequences
Transcriptional Activation of Endogenous Retroviral Sequences in Human Epidermal Keratinocytes by UVB Irradiation.
Ultraviolet radiation is a pathogenic factor in various diseases, e.g., autoimmune disorders such as lupus erythematosus. On the other hand, endogenous retroviruses are discussed as etiologic agents in lupus erythematosus. Therefore, we investigated the influence of ultraviolet irradiation on expression of human endogenous retroviral sequences and human endogenous retroviral sequence promoter-driven transcription of cellular genes using human epidermal keratinocytes as a model system. First, conserved sequences of endogenous retroviral pol genes were amplified from cellular mRNA by reverse transcriptase polymerase chain reaction with degenerate oligonucleotide primers. Polymerase chain reaction products were hybridized in a reverse dot blot hybridization assay to a representative number of distinct cloned human endogenous retroviral pol fragments. Using this method, we could show that irradiation with 30 mJ per cm2 ultraviolet B activates transcription of various endogenous retroviral pol sequences in primary epidermal keratinocytes as well as in a spontaneously immortalized keratinocyte cell line (HaCaT). Interestingly, some of these sequences were found to be closely related to pol sequences of human endogenous retroviral sequences which have been shown to be expressed in autoimmune patients. Analysis of human endogenous retroviral pol expression in vivo using skin biopsies of lupus erythematosus patients revealed similar activation patterns. In a second approach, ultraviolet B- induced chimeric transcripts were isolated which are initiated by human endogenous retroviral promoters and proceed into cellular sequences using a newly established modified differential display polymerase chain reaction technique. The activation of human endogenous retroviral sequence transcription by ultraviolet B may contribute to the pathogenesis of lupus erythematosus, where inappropriate antigenic presentation of ultraviolet B-induced viral and cellular proteins could stimulate autoantibody production
Klinisch-biomedizinische Forschung an ausseruniversitaeren Einrichtungen der biomedizinischen Grundlagenforschung in Kooperation mit Hochschulkliniken KBF. Teilprojekt: Aktivierung endogener retroviraler Gene bei Autoimmunerkrankungen Schlussbericht
Available from TIB Hannover: F00B1332 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung und Forschung, Berlin (Germany)DEGerman