CO-EXPRESSION OF DISTINCT COILED COILS CAN LEAD TO THEIR ENTANGLEMENT

Abstract

L1 (LINE1) non-LTR retrotransposons are ubiquitous genomic parasites and the dominant transposable element in humans having generated about 40% of their genomic DNA during their [~]100 million years (Myr) of activity in primates. L1 replicates in early embryos, causing genetic diversity and defects, but can be active in some somatic stem cells, tumors and during aging. L1 encodes two proteins essential for retrotransposition: ORF2, a replicase, and ORF1, a coiled coil mediated homo trimer, which functions as a nucleic acid chaperone. Both proteins contain highly conserved domains and preferentially bind their encoding transcript to form an L1 ribonucleoprotein (RNP), which mediates retrotransposition. However, the coiled coil has undergone episodes of substantial amino acid replacement to the extent that a given L1 family can concurrently express multiple ORF1s that differ in the sequence of their coiled coils. Here we show that such distinct ORF1p sequences can become entangled forming heterotrimers when co-expressed from separate vectors.