Revisiting the impact of synthetic ORF sequences on engineered LINE-1 retrotransposition.

Synthetic mouse L1 with reduced ORF adenosine content and specific sequence modifications shows significantly increased retrotransposition efficiency compared to native L1spa.

• Why it matters: Understanding factors that influence L1 retrotransposition is crucial because it affects genome stability and evolution; the impact of sequence features like the GRR and ORF modifications remains unclear.
• What they did: Researchers compared native and synthetic L1 sequences, identifying the combined effect of amino acid changes and the deletion of the GRR 3'UTR on retrotransposition, and examined how the GRR influences natural L1 activity.
• The result: The study found that the GRR affects natural L1 retrotransposition through modulation of ORF1p abundance in a position-dependent manner, but synthetic L1s bypass this inhibition, highlighting the influence of sequence arrangement on retrotransposition efficiency.