Alu expression in human cell lines and their retrotranspositional potential
- Equal contributors
1 Tulane Cancer Center SL-66, Dept. of Epidemiology, Tulane University, 1430 Tulane Ave, New Orleans, LA 70112, USA
2 Department of Oncological Sciences, Huntsman Cancer Institute, and Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, UT USA
3 Center for Integrative Genomics (CIG), Faculty of Biology and Medicine, University of Lausanne, Lausanne 1015, Switzerland
4 Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Mobile DNA 2012, 3:11 doi:10.1186/1759-8753-3-11Published: 20 June 2012
The vast majority of the 1.1 million Alu elements are retrotranspositionally inactive, where only a few loci referred to as ‘source elements’ can generate new Alu insertions. The first step in identifying the active Alu sources is to determine the loci transcribed by RNA polymerase III (pol III). Previous genome-wide analyses from normal and transformed cell lines identified multiple Alu loci occupied by pol III factors, making them candidate source elements.
Analysis of the data from these genome-wide studies determined that the majority of pol III-bound Alus belonged to the older subfamilies Alu S and Alu J, which varied between cell lines from 62.5% to 98.7% of the identified loci. The pol III-bound Alus were further scored for estimated retrotransposition potential (ERP) based on the absence or presence of selected sequence features associated with Alu retrotransposition capability. Our analyses indicate that most of the pol III-bound Alu loci candidates identified lack the sequence characteristics important for retrotransposition.
These data suggest that Alu expression likely varies by cell type, growth conditions and transformation state. This variation could extend to where the same cell lines in different laboratories present different Alu expression patterns. The vast majority of Alu loci potentially transcribed by RNA pol III lack important sequence features for retrotransposition and the majority of potentially active Alu loci in the genome (scored high ERP) belong to young Alu subfamilies. Our observations suggest that in an in vivo scenario, the contribution of Alu activity on somatic genetic damage may significantly vary between individuals and tissues.