Activation of expression of multiple subfamilies of human Alu elements by adenovirus type 5 and herpes simplex virus type 1.
ABSTRACT The nearly one million Alu repetitive elements in the human genome can be grouped into a number of subfamilies. Comparisons between subfamily consensus sequences suggest that Alu evolution is characterized by the sequential amplification and dispersal of a limited number of Alu founder sequences. The S, Sb and Sb1 subfamilies provide an example of such a related series of Alu subfamilies. We have previously demonstrated that adenovirus type 5 and herpes simplex virus type 1 activate RNA polymerase III transcription of endogenous Alu elements in HeLa cells. Here, we report that expression of Alu sequences belonging to the S, Sb and Sb1 subfamilies was activated following infection with these viruses. The data indicate that transpositionally inactive Alu elements can give rise to high levels of pol III transcripts in the presence of appropriate trans-acting factors and demonstrate that the class III promoters of a significant number and variety of Alu sequences are functional in vivo. Multiple subfamilies of Alu sequences were induced in transformed and non-transformed cell types, suggesting that induction of Alu expression may be part of the normal cellular response to viral infection.
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ABSTRACT: Mobile elements account for almost half of the mass of the human genome. Only the retroelements from the non-LTR (long terminal repeat) retrotransposon family, which include the LINE-1 (L1) and its non-autonomous partners, are currently active and contributing to new insertions. Although these elements seem to share the same basic amplification mechanism, the activity and success of the different types of retroelements varies. For example, Alu-induced mutagenesis is responsible for the majority of the documented instances of human disease induced by insertion of retroelements. Using copy number in mammals as an indicator, some SINEs have been vastly more successful than other retroelements, such as the retropseudogenes and even L1, likely due to differences in post-insertion selection and ability to overcome cellular controls. SINE and LINE integration can be differentially influenced by cellular factors, indicating some differences between in their amplification mechanisms. We focus on the known aspects of this group of retroelements and highlight their similarities and differences that may significantly influence their biological impact.Frontiers in Bioscience 01/2012; 17:1345-61. · 3.29 Impact Factor
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ABSTRACT: Editing of RNA molecules gained major interest when coding mRNA was analyzed. A small, noncoding, Alu DNA element transcript that may act as regulatory RNA in cells was examined in this study. Alu DNA element transcription was determined in buffy coat from healthy humans and human sporadic Creutzfeldt-Jakob disease (sCJD) cases. In addition, non-sCJD controls, mostly dementia cases and Alzheimer's disease (AD) cases, were included. The Alu cDNA sequences were aligned to genomic Alu DNA elements by database search. A comparison of best aligned Alu DNA sequences with our RNA/cDNA clones revealed editing by deamination by ADAR (adenosine deaminase acting on RNA) and APOBEC (apolipoprotein B editing complex). Nucleotide exchanges like a G instead of an A or a T instead of a C in our cDNA sequences versus genomic Alu DNA pointed to recent mutations. To confirm this, our Alu cDNA sequences were aligned not only to genomic human Alu DNA but also to the respective genomic DNA of the chimpanzee and rhesus. Enhanced ADAR correlated with A-G exchanges in dementia, AD, and sCJD was noted when compared to healthy controls as well as APOBEC-related C-T exchanges. The APOBEC-related mutations were higher in healthy controls than in cases suffering from neurodegeneration, with the exception of the dementia group with the prion protein gene (PRNP) MV genotype. Hence, this study may be considered the first real-time analysis of Alu DNA element transcripts with regard to editing of the respective Alu transcripts in human blood cells.Journal of Toxicology and Environmental Health Part A 01/2011; 74(2-4):88-95. · 1.73 Impact Factor