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Published on: November 2, 2013
Tissue-specific expression of human provirus ERV3 mRNA in human placenta: two of the three ERV3 mRNAs contain human
Abstract:
Three polyadenylated RNAs, 9, 7.3, and 3.5 kilobases long, of a human endogenous retrovirus, ERV3, are abundant in human placental chorion, representing about 0.03 to 0.05% of the total mRNA. We characterized the structure of these mRNAs by Northern blot and S1 nuclease mapping analyses. We found that all three RNAs were spliced mRNAs that lacked 5.9 kilobases of proviral sequence, including the gag gene and most of the pol gene. In contrast to the transcription pattern usual for other retroviruses, the transcription pattern of the ERV3 provirus did not include a genome-length mRNA. All three of the ERV3 mRNAs initiated transcription at the same point in the 5' long terminal repeat (LTR) and contained identical splice junctions in the provirus. The 3.5-kilobase RNA was a typical subgenomic proviral mRNA, with its polyadenylation site in the 3' LTR. The two larger ERV3 mRNAs, however, extended through the polyadenylation site in the 3' LTR and were spliced at a second position approximately 370 nucleotides downstream from the 3' LTR. This finding suggests that when the ERV3 retrovirus integrated at this genomic locus in an ancestor of humans, it integrated within or adjacent to a cellular gene.
Insights
Human endogenous retrovirus 3 (ERV3) produces abundant spliced mRNAs in the placenta. These transcripts lack key retroviral genes, suggesting ERV3 integrated near a cellular gene in early human ancestors.
Area of Science:
- Molecular Biology
- Genomics
- Virology
Background:
- Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections integrated into the host genome.
- ERV3 is a specific HERV family with transcripts detected in placental tissues.
- Understanding HERV transcription and structure is crucial for deciphering their role in human biology and evolution.
Purpose of the Study:
- To characterize the structure and transcription pattern of abundant ERV3-specific mRNAs found in human placental chorion.
- To investigate the implications of ERV3 mRNA structure for its genomic integration and potential functional role.
Main Methods:
- Northern blot analysis to determine RNA size and abundance.
- S1 nuclease mapping to precisely map the transcription start sites and splice junctions of ERV3 mRNAs.
- Analysis of proviral sequence and long terminal repeat (LTR) regions.
Main Results:
- Three abundant polyadenylated ERV3 mRNAs (9, 7.3, and 3.5 kb) were identified in placental chorion mRNA.
- All three ERV3 mRNAs are spliced and significantly truncated, lacking the gag gene and most of the pol gene.
- Unlike typical retroviruses, no genome-length ERV3 mRNA was detected.
- Two larger ERV3 mRNAs exhibited unusual splicing beyond the 3' LTR polyadenylation site, suggesting integration adjacent to a cellular gene.
Conclusions:
- ERV3 transcription in the placenta yields spliced, truncated mRNAs, deviating from canonical retroviral expression patterns.
- The unique splicing of larger ERV3 mRNAs strongly implies that the ERV3 provirus integrated within or near a host cellular gene.
- These findings provide insights into the expression of endogenous retroviruses and their genomic context in humans.
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