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Alu Elements: Where Do They Come From, Where Do They Go?

In order to replicate, Alu elements are transcribed into RNA which folds into a secondary structure and attaches itself to the ribosome’s exit tunnel. Once a LINE1 retrotransposon is translated, the Alu RNA hijacks the LINE1 retrotransposition mechanism to be reinserted into the genome.

Our work aims to understand the connection between the reproductive success of Alu elements and their sequence characteristics. With an average size of 300 nucleotides and a frequency of one million, Alu elements are the most abundant retrotransposable elements in the human genome.

While Alu elements contain a bipartite RNA polymerase III (Pol III) promoter, it is under debate if they are Pol III or Pol II transcripts. E.g., we do not observe a significant correlation between Pol III binding to the DNA and Alu transcription. Using a multiple alignment of all Alu sequences and a Generalized Linear Model (respectively Random Forest), we relate Alu sequence variation to transcription activity.

We apply metabolic RNA labeling to measure Alu transcription and degradation rates under standard and Pol II inhibiting conditions. We find strong evidence that Alu transcription is not a side product of Pol II gene transcription. Further, Alu transcripts appear to be surprisingly stable with an average half-life exceeding one hour. Lastly, we identify several loci in the Alu consensus sequence that are particularly relevant to Alu transcription.