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Published on: November 3, 2013
Identification of a retinoic acid-inducible endogenous retroviral transcript in the human teratocarcinoma-derived
P Kannan1, R Buettner, D R Pratt
1Department of Tumor Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Abstract:
Retinoic acid (RA), a developmental morphogen, causes activation of a transcript of an endogenous retrovirus-related element in the human teratocarcinoma-derived cell line PA-1. This provirus is defective, and the provirus-related sequences exist as multicopy elements (more than 20 copies) in human DNA. This is the first human endogenous retroviral mRNA that is known to be transcriptionally activated by RA. The nucleotide sequence of the 3,357 bp of this viral cDNA was determined and shows a strong homology to the type C-related human endogenous retroviral proviruses ERV3 and 4-1. This cDNA contains 'R-U5-delta pol-env-U3-R sequences of the provirus. Adjacent to the putative 5' long terminal repeat of this provirus there is an 18-bp sequence complementary to the 3' end of isoleucine tRNA. We named this RA-responsive virus RRHERV-I.
Insights
Retinoic acid (RA) activates a novel human endogenous retrovirus (RRHERV-I) in PA-1 cells. This defective provirus, found in multiple copies in human DNA, represents the first RA-inducible human endogenous retroviral mRNA.
Area of Science:
- Molecular Biology
- Virology
- Genetics
Background:
- Retinoic acid (RA) is a crucial developmental morphogen.
- Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections integrated into the host genome.
- The transcriptional regulation of HERVs by developmental factors is not fully understood.
Purpose of the Study:
- To investigate the effect of retinoic acid (RA) on endogenous retroviral elements in human cells.
- To characterize a novel RA-responsive human endogenous retrovirus.
Main Methods:
- RA treatment of human teratocarcinoma-derived PA-1 cells.
- Analysis of retroviral transcript activation.
- Determination of the nucleotide sequence of the viral cDNA.
- Homology analysis with known HERV sequences.
Main Results:
- RA induced the transcription of a defective endogenous retrovirus-related element in PA-1 cells.
- This element, named RRHERV-I, exists as multicopy elements in human DNA.
- The 3,357 bp cDNA sequence showed homology to ERV3 and 4-1 HERVs.
- The cDNA contained characteristic retroviral sequences (R-U5-delta pol-env-U3-R) and a tRNA-binding site.
Conclusions:
- RRHERV-I is the first identified human endogenous retroviral mRNA transcriptionally activated by RA.
- RA-inducible HERVs may play a role in human development or cellular processes.
- Further research into RRHERV-I function and regulation is warranted.
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