Cellular biology of hominoid-specific composite retrotransposons in an evolutionary perspective

• Applicant: Dr. Annette Damert
• Subject Area: Evolutionary Cell and Developmental Biology (Zoology) ; Evolution, Anthropology ; Cell Biology
• Term: from 2017 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 387502000

SVA (SINE-R-VNTR-Alu) and LAVA (L1-Alu-VNTR-Alu) are non-autonomous non-LTR retrotransposons specific to hominoid primates. LAVA amplified in gibbons only; SVA expanded in great apes. Different great ape lineages (orangutan, chimpanzee, human) are characterized by the presence of structurally distinct SVA subfamilies with different amplification dynamics in evolution. The molecular basis for this is not known. Both SVA and LAVA can be mobilized by the LINE1 (L1)-encoded protein machinery in trans. Sequence-based structural determinants of mobilization efficiency differ between SVA and LAVA. The intracellular fate of the RNA intermediates of SVA/LAVA between transcription and incorporation into the L1 RNP has not been explored. In a comparative approach the project will address the molecular mechanisms underlying the differences in SVA/LAVA amplification dynamics across hominoid primates. The first objective of the project is to test the hypothesis that the interaction with different sets of host proteins provides the molecular basis for the differences in SVA/LAVA structural requirements for mobilization and contributes to the expansion of only one of the two families in humans and gibbons, respectively. The protein interactomes of SVA and LAVA RNA will be characterized in human and gibbon cells with regard to their function in the regulation of RNA turnover and in retrotransposition of SVA/LAVA by L1-encoded proteins in trans. The second objective of the project aims at establishing whether possible preferential interactions between the currently expanding SVA/LAVA subfamilies and the currently active L1 subfamily of the same species are involved in the species-specific amplification of structurally distinct families/subfamilies. It will also address the question to what extent the host factor environment contributes to such preferential interactions.

• DFG Programme: Research Grants