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LINE-mediated retrotransposition of marked Alu sequences
Marie Dewannieux1, Cécile Esnault, Thierry Heidmann
1Unité des Rétrovirus Endogènes et Eléments Rétroïdes des Eucaryotes Supérieurs, UMR 8122 CNRS, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France.
Nature Genetics
|August 5, 2003
Summary
Alu elements, common human transposons, can move within the genome through retrotransposition. This process requires LINEs and a poly-A tail, explaining their high mutation rate.
Area of Science:
- Molecular Biology
- Genetics
- Genomics
Background:
- Alu elements are abundant, non-coding DNA sequences in the human genome.
- They are transcribed by RNA polymerase III (Pol III) and are known to transpose.
- Previous work demonstrated LINEs' ability to retrotranspose mRNA transcripts.
Purpose of the Study:
- To investigate the retrotransposition mechanism of Alu elements.
- To identify factors essential for Alu mobility.
- To quantify the retroposition rate of Alu transcripts.
Main Methods:
- Introduction of marked Alu sequences with an autocatalytic intron into human HeLa cells.
- Analysis of integration sites and associated genomic features.
- Assessment of the role of LINEs and the 3' poly-A stretch in Alu transposition.
Main Results:
- Demonstrated Alu sequence mobility exhibiting hallmarks of retrotransposition, including intron splicing and target site duplications.
- Identified the 3' poly-A stretch as critical for Alu mobility.
- Confirmed the necessity of LINEs for Alu transposition.
- Observed Alu transcript retroposition rates 100-1,000 times higher than control mRNAs.
Conclusions:
- Alu elements retrotranspose via a mechanism dependent on LINEs and their own 3' poly-A tail.
- This efficient retrotransposition mechanism accounts for the high mutational activity of Alu elements in the human genome.