Retroelements and Genetic Instability in Breast Cancer
Abstract
LINEl is the most prevalent human retroelement and it contributes to genomic instability. The full extent of LINE-1 mobility in somatic tissues and tumors is not known. L1 expression is extremely low in differentiated cells except for testis but it is significantly elevated in some breast cancer cells. Full-length LINE-1 RNA is not detected even when transiently expressed from the CMV promoter. These observations suggest that posttranscriptional mechanisms are involved in limitation of L1 expression. By using a polyadq program we identified 20 putative polyadenylation (polyA) sites located only in the sense strand of the L1.3 genome. We hypothesize that the use of the putative polyA sites located within the L1 .3 genome limit the amount of full-length L1 .3 niRNAs present in mammalian cells. We developed a system that allows detection of the full-length L1 mRNA and any RNA species produced through internal polyadenylation. We determined that numerous putative polyadenylation sites found in L1 elements are functional and they attenuate full-length L1 RNA formation by about 50 fold. There is tremendous redundancy in these internal polyadenylation sites. This unique attenuation mechanism helps to minimize the rate of L1 retrotransposition but may also increase the negative impact of these insertion events on the genome.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2003
- Accession Number
- ADA424037
Entities
People
- Victoria P. Perepelitsa
Organizations
- Tulane University of Louisiana