RECENT FINDINGS: How L1 &its host interact it largely unknown. We examined two possible examples: (1) Adaptive evolution of ORF1p - ORF1p, one of two L1 encoded proteins, underwent adaptive evolution in recent primate history (Boissinot, et al, Mol. Biol. Evol. 18: 2186) . Adaptive evolution can reflect a biological interaction (e.g., as between a virus &its host). Although both yeast and mammalian two-hybrid assays showed that some host proteins interact with ORF1p, we showed that these host proteins are all highly conserved during evolution. Thus, these host proteins are not the likely target of the adaptive evolution of ORF1p. We are now pursuing other """"""""targets"""""""" of the adaptive response of ORF1p. (2) L1 RNA transport - Others showed that the nuclear exchange factor (NXF1) binds a region of L1 RNA. NXF1 is a host protein that shuttles RNAs in &out of the nucleus. Our evolutionary analysis showed that the L1 NXF1-binding site (part of which does not encode protein) has been highly conserved over 60 Myr of L1-evolution in primates. However, extensive experiments in collaboration with Marie-Louise Hammarskjld now show that NXF1 does NOT reproducibly affect L1 RNA transport. Therefore, we have discontinued this portion of the project.
